• Cancer vaccine
• Clinical trial
• DNA
• Neoantigens
• Tumor antigens
• mRNA

• Humans
• Cancer Vaccines/immunology
• Cancer Vaccines/therapeutic use
• Precision Medicine/methods
• Antigens, Neoplasm/immunology
• Neoplasms/immunology
• Neoplasms/therapy
• Vaccine Development/methods
• Nucleic Acids/immunology
• Immunotherapy/methods

• P50 CA098252 NCI NIH HHS
• P50CA098252 Foundation for the National Institutes of Health

• CTA
• NY-ESO-1
• cancer vaccine
• immunotherapy
• solid cancer

• Male
• Humans
• Cancer Vaccines
• CD8-Positive T-Lymphocytes
• Antibodies
• Immunotherapy
• Bacterial Vaccines
• Neoplasms/therapy

• Antigen delivery system
• Extracellular vesicle
• Nanoparticle
• Self-assembled particles
• Vaccine
• Vector

• exosome
• nanocarriers
• nanoparticles
• nanovaccine

Recently, the interest in using nucleic acids for therapeutic applications has been increasing. DNA molecules can be manipulated to express a gene of interest for gene therapy applications or vaccine development. Plasmid DNA can be developed to treat different diseases, such as infections and cancer. In most cancers, the immune system is limited or suppressed, allowing cancer cells to grow. DNA vaccination has demonstrated its capacity to stimulate the immune system to fight against cancer cells. Furthermore, plasmids for cancer gene therapy can direct the expression of proteins with different functions, such as enzymes, toxins, and cytotoxic or proapoptotic proteins, to directly kill cancer cells. The progress and promising results reported in animal models in recent years have led to interesting clinical results. These DNA strategies are expected to be approved for cancer treatment in the near future. This review discusses the main strategies, challenges, and future perspectives of using plasmid DNA for cancer treatment.

• DNA vaccination
• apoptosis
• cancer
• gene therapy
• non-viral gene therapy
• plasmid optimization
• plasmids
• tumor-specific antigens
• tumor-specific promoters

NY‐ESO‐1 is a cancer/testis antigen expressed in various cancer types. However, the induction of NY‐ESO‐1‐specific CTLs through vaccines is somewhat difficult. Thus, we developed a new type of artificial adjuvant vector cell (aAVC‐NY‐ESO‐1) expressing a CD1d‐NKT cell ligand complex and a tumor‐associated antigen, NY‐ESO‐1. First, we determined the activation of invariant natural killer T (iNKT) and natural killer (NK) cell responses by aAVC‐NY‐ESO‐1. We then showed that the NY‐ESO‐1‐specific CTL response was successfully elicited through aAVC‐NY‐ESO‐1 therapy. After injection of aAVC‐NY‐ESO‐1, we found that dendritic cells (DCs) in situ expressed high levels of costimulatory molecules and produced interleukn‐12 (IL‐12), indicating that DCs undergo maturation in vivo. Furthermore, the NY‐ESO‐1 antigen from aAVC‐NY‐ESO‐1 was delivered to the DCs in vivo, and it was presented on MHC class I molecules. The cross‐presentation of the NY‐ESO‐1 antigen was absent in conventional DC‐deficient mice, suggesting a host DC‐mediated CTL response. Thus, this strategy helps generate sufficient CD8⁺ NY‐ESO‐1‐specific CTLs along with iNKT and NK cell activation, resulting in a strong antitumor effect. Furthermore, we established a human DC‐transferred NOD/Shi‐scid/IL‐2γc^null immunodeficient mouse model and showed that the NY‐ESO‐1 antigen from aAVC‐NY‐ESO‐1 was cross‐presented to antigen‐specific CTLs through human DCs. Taken together, these data suggest that aAVC‐NY‐ESO‐1 has potential for harnessing innate and adaptive immunity against NY‐ESO‐1‐expressing malignancies.

• NKT cell
• cancer
• cytotoxic T cell
• dendritic cells
• immunotherapy

• Vaccine
• cancer-testis antigen
• first-in-human
• pulmonary metastasis
• thoracic malignancy

• U01 DK124165 NIDDK NIH HHS
• U24 CA224319 NCI NIH HHS
• ZIA SC010093 Intramural NIH HHS

The only vaccine approved by FDA as a treatment for cancer is sipuleucel-T, a therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). Most investigators studying anti-tumor vaccines believe they will be most effective as parts of combination therapies, rather than used alone. Unfortunately, the cost and complexity of sipuleucel-T makes it difficult to feasibly be used in combination with many other agents. In this review article we discuss the use of DNA vaccines as a simpler vaccine approach that has demonstrated efficacy in several animal species. We discuss the use of DNA vaccines in combination with traditional treatments for mCRPC, and other immune-modulating treatments, in preclinical and early clinical trials for patients with mCRPC.

Metastatic castration-resistant prostate cancer (mCRPC) is a challenging disease to treat, with poor outcomes for patients. One antitumor vaccine, sipuleucel-T, has been approved as a treatment for mCRPC. DNA vaccines are another form of immunotherapy under investigation. DNA immunizations elicit antigen-specific T cells that cause tumor cell lysis, which should translate to meaningful clinical responses. They are easily amenable to design alterations, scalable for large-scale manufacturing, and thermo-stable for easy transport and distribution. Hence, they offer advantages over other vaccine formulations. However, clinical trials with DNA vaccines as a monotherapy have shown only modest clinical effects against tumors. Standard therapies for CRPC including androgen-targeted therapies, radiation therapy and chemotherapy all have immunomodulatory effects, which combined with immunotherapies such as DNA vaccines, could potentially improve treatment. In addition, many investigational drugs are being developed which can augment antitumor immunity, and together with DNA vaccines can further enhance antitumor responses in preclinical models. We reviewed the literature available prior to July 2020 exploring the use of DNA vaccines in the treatment of prostate cancer. We also examined various approved and experimental therapies that could be combined with DNA vaccines to potentially improve their antitumor efficacy as treatments for mCRPC.

• DNA vaccine
• IDO inhibitor
• TLR agonist
• androgen deprivation
• chemotherapy
• combination therapy
• immune checkpoint blockade
• prostate cancer
• radiation

• R01 CA219154 NCI NIH HHS
• T32 GM008692 NIGMS NIH HHS
• R01 CA219154 NIH HHS

• DNA tattooing
• ballistic delivery
• electroporation
• intradermal
• microneedles
• skin permeabilization
• transcutaneous
• vaccine

• EP/L016494/1 Engineering and Physical Sciences Research Council
• EP/L024012/1 EPSRC Centre for Doctoral Training in Medical Imaging

• DNA vaccine
• adjuvant
• immune cell targeting
• nanoparticle
• nanotechnology
• peptide vaccine
• vaccine

• T-cell responses
• cancer vaccine
• immunotherapy
• long synthetic peptide
• tumor associated survivin antigen

• CD8+ T cells
• Cancer vaccine
• Checkpoint inhibitor
• Resident memory T cells
• Therapeutic combination
• Tumor antigens

• Animals
• Antigens, Neoplasm/immunology
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/metabolism
• Cancer Vaccines/administration & dosage
• Cancer Vaccines/immunology
• Cross-Priming
• Humans
• Immunologic Memory
• Immunotherapy/methods
• Immunotherapy, Adoptive/methods
• Neoplasms/immunology
• Neoplasms/metabolism
• Neoplasms/therapy
• Signal Transduction
• Treatment Outcome

• adoptive cell transfer
• checkpoint inhibition
• immune modulators
• immune surveillance
• oncolytic viruses
• vaccination

• MR/M015564/1 Medical Research Council

• Animals
• Autoantigens/immunology
• Autoimmune Diseases/immunology
• Autoimmune Diseases/therapy
• Autoimmunity
• Epitope Mapping
• Epitopes, T-Lymphocyte/immunology
• Humans
• Immunomodulation
• Immunotherapy
• Neoplasms/immunology
• Neoplasms/therapy
• T-Lymphocyte Subsets/immunology
• T-Lymphocyte Subsets/metabolism
• T-Lymphocytes, Helper-Inducer/immunology
• T-Lymphocytes, Helper-Inducer/metabolism
• Th1 Cells/immunology
• Th1 Cells/metabolism
• Th2 Cells/immunology
• Th2 Cells/metabolism
• Vaccines/administration & dosage
• Vaccines/immunology

DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, identification of neoantigens, mutanome studies, designing fusion plasmids, vaccine adjuvant modifications, and co-treatment with immune-checkpoint inhibitors. In this review, we follow a Porter’s analysis analogy, otherwise commonly used in business models, to analyze various immune-forces that determine the potential success and sustainable positive outcomes following DNA vaccination using non-viral tumor associated antigens in treatment against cancer.

• DNA vaccine
• T-cells
• cytokines
• immune checkpoint inhibitors
• tumor associated antigens

• DNA vaccines
• Immunotherapy
• Mechanism of action
• Prostate cancer

• AFP, α-fetoprotein
• APCs, antigen presenting cells
• CEA, carcinoembryonic antigen
• CTLA-4, cytotoxic T lymphocyte-associated antigen-4
• DCs, dendritic cells
• DNA vaccine
• EP, electroporation
• GITR, glucocorticoid-induced tumor necrosis factor receptor family-related gene
• HPV, human papillomavirus
• HSP, heat shock protein
• HSV, herpes simplex virus
• ID, intradermal
• IM, intramuscular
• MAGE, melanoma-associated antigen
• MART, melanoma antigen recognized by T cells
• PAP, prostatic acid phosphatase
• PD, programmed death
• PRAME, preferentially expressed antigen in melanoma
• PSA, prostate-specific antigen
• PSMA, prostate-specific membrane antigen
• WT1, Wilm's tumor
• anti-tumor immunity
• cancer
• hTERT, human telomerase reverse transcriptase
• tumor immune evasion

• cancer vaccines
• melanoma
• cyclophosphamide
• regulatory t cells

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm/immunology
• Antineoplastic Agents, Alkylating/administration & dosage
• CD4-Positive T-Lymphocytes/immunology
• Cancer Vaccines/administration & dosage
• Cancer Vaccines/immunology
• Cholesterol/immunology
• Cohort Studies
• Combined Modality Therapy
• Cyclophosphamide/administration & dosage
• Dose-Response Relationship, Drug
• Drug Combinations
• Female
• Follow-Up Studies
• Humans
• Lymphatic Metastasis
• Male
• Melanoma/immunology
• Melanoma/secondary
• Melanoma/therapy
• Membrane Proteins/immunology
• Middle Aged
• Neoplasm Staging
• Phospholipids/immunology
• Prognosis
• Saponins/immunology
• T-Lymphocytes, Regulatory/immunology

• bladder cancer
• radical cystectomy
• perioperative chemotherapy
• perioperative targeted therapy
• mtor inhibitor
• immune therapy
• gene therapy
• vaccine therapy

• Antineoplastic Agents/therapeutic use
• Cancer Vaccines/therapeutic use
• Chemotherapy, Adjuvant
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Cystectomy
• Genetic Therapy
• Humans
• Molecular Targeted Therapy
• Muscle, Smooth
• Neoadjuvant Therapy
• Neoplasm Invasiveness
• Perioperative Care
• TOR Serine-Threonine Kinases/antagonists & inhibitors
• Urinary Bladder Neoplasms/pathology
• Urinary Bladder Neoplasms/therapy

A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2.

The adjuvant effects of APH were examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic models. We further determined the immunogenicity and anti-tumor effect of NY-ESO-1-APH (NAPH) vaccine using adoptive cellular/serum therapy in C57/B6 and nude mice. Cell-mediated and antibody-mediated immune responses were evaluated.

The APH complex significantly promoted antigen uptake, maturation and cross-presentation of dendritic cells and enhanced the secretion of TNF-α, MCP-1 and IFN-γ by human peripheral blood mononuclear cells compared with individual components. Vaccination of NAPH resulted in significant tumor regression or delayed tumor progression in prophylactic and therapeutic models. In addition, passive serum/cellular therapy potently inhibited tumor growth of NY-ESO-1-B16. Mice treated with NAPH vaccine produced higher antibody titers and greater antibody-dependent/independent cellular cytotoxicity. Therefore, NAPH vaccination effectively stimulated innate immunity, and boosted both arms of the adaptive humoral and cellular immune responses to suppress tumorigenesis and growth of melanoma.

Our study revealed the potential application of APH complex as a novel immunomodulatory agent for vaccines against tumor refractory and growth.

• Clinical trials
• DNA vaccines
• Prostate cancer
• Tumor vaccine

• breast cancer
• cancer-testis antigen
• ny-br-1
• immunotherapy
• prognosis

• Antigens, Neoplasm/analysis
• Antigens, Neoplasm/biosynthesis
• Biomarkers, Tumor/analysis
• Breast Neoplasms/metabolism
• Breast Neoplasms/mortality
• Breast Neoplasms/pathology
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Tissue Array Analysis

While immune monitoring of tumor immunotherapy often focuses on the generation of productive Th1-type inflammatory immune responses, the importance of regulatory immune responses is often overlooked, despite the well-documented effects of regulatory immune responses in suppressing anti-tumor immunity. In a variety of malignancies, the frequency of regulatory cell populations has been shown to correlate with disease progression and a poor prognosis, further emphasizing the importance of characterizing the effects of immunotherapy on these populations. This review focuses on the role of suppressive immune populations (regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages) in inhibiting anti-tumor immunity, how these populations have been used in the immune monitoring of clinical trials, the prognostic value of these responses, and how the monitoring of these regulatory responses can be improved in the future.

• immune monitoring
• myeloid-derived suppressor cells
• predictors of response
• regulatory T cells
• suppression
• tolerance

• DNA vaccines
• cancer testis antigens
• cytotoxic T cells
• tumor peptides

• Antigen-Presenting Cells/immunology
• Antigen-Presenting Cells/metabolism
• Antigens, Neoplasm/administration & dosage
• Antigens, Neoplasm/immunology
• CD4 Antigens/metabolism
• Cancer Vaccines/administration & dosage
• Cancer Vaccines/immunology
• Exudates and Transudates/immunology
• Humans
• Immunosuppression Therapy
• Interleukin-12/pharmacology
• Interleukin-2 Receptor alpha Subunit/metabolism
• Membrane Proteins/administration & dosage
• Membrane Proteins/immunology
• Neoplasms/immunology
• Picibanil/administration & dosage
• Picibanil/immunology
• Streptococcus pyogenes/immunology
• T-Lymphocytes, Regulatory/drug effects
• T-Lymphocytes, Regulatory/immunology
• T-Lymphocytes, Regulatory/metabolism

Antigen-specific anti-tumor vaccines have demonstrated clinical efficacy, but immunological and clinical responses appear to be patient-dependent. We hypothesized that naturally-occurring differences in amino acid sequence of a host’s target antigen might predict for immunological outcome from genetic vaccination by presentation of epitopes different from the vaccine.

Using peripheral blood cells from 33 patients who had been treated with a DNA vaccine encoding prostatic acid phosphatase (PAP), we sequenced the exons encoding PAP and PSA genes from somatic DNA to identify single nucleotide polymorphisms. In addition, mRNA was collected to detect alternative splice variants of PAP.

We detected four synonymous coding mutations of PAP among 33 patients; non-synonymous coding mutations were not identified. Alternative splice variants of PAP were detected in 22/27 patients tested. The presence of detectable splice variants was not predictive of immunological outcome from vaccination. Immune responses to peptides encoded by these splice variants were common (16/27) prior to immunization, but not associated with immune responses elicited with vaccination.

These results suggest that antigen-specific immune responses detectable after treatment with this genetic vaccine are specific for the host-encoded antigen and not due to epitope differences between the vaccine and a particular individual’s somatic coding sequence.

• Allelic variants
• Alternative splice variants
• DNA vaccines
• PAP

Ovarian cancer is the leading cause of death from gynaecological malignancy. Despite improved detection and treatment options, relapse rates remain high. Combining immunotherapy with the current standard treatments may provide an improved prognosis, however, little is known about how standard chemotherapy affects immune potential (particularly T cells) over time, and hence, when to optimally combine it with immunotherapy (e.g., vaccines). Herein, we assess the frequency and ratio of CD8+ central memory and effector T cells as well as CD4+ effector and regulatory T cells (Tregs) during the first 18 weeks of standard chemotherapy for ovarian cancer patients. In this pilot study, we observed increased levels of recently activated Tregs with tumor migrating ability (CD4+CD25^hiFoxp3+CD127−CCR4+CD38+ cells) in patients when compared to controls. Although frequency changes of Tregs as well as the ratio of effector T cells to Tregs were observed during treatment, the Tregs consistently returned to pre-chemotherapy levels at the end of treatment. These results indicate T cell subset distributions associated with recurrence may be largely resistant to being “re-set” to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients.

• Adjuvants, Immunologic
• Animals
• Antigens, Neoplasm/immunology
• CD4-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/immunology
• Cancer Vaccines/immunology
• Humans
• Immunity, Cellular/immunology
• Melanoma/immunology
• Melanoma/metabolism
• Membrane Proteins/immunology
• Mice
• T-Lymphocytes/immunology
• Trypanosoma cruzi/immunology

AIM: To investigate the immunological repertoire in the peritoneal cavity of gastric cancer patients.

METHODS: The peritoneal cavity is a compartment in which immunological host-tumor interactions can occur. However, the role of lymphocytes in the peritoneal cavity of gastric cancer patients is unclear. We observed 64 patients who underwent gastrectomy for gastric cancer and 11 patients who underwent laparoscopic cholecystectomy for gallstones and acted as controls. Lymphocytes isolated from both peripheral blood and peritoneal lavage were analyzed for surface markers of lymphocytes and their cytokine production by flow cytometry. CD4⁺CD25^high T cells isolated from the patient’s peripheral blood were co-cultivated for 4 d with the intra-peritoneal lymphocytes, and a cytokine assay was performed.

RESULTS: At gastrectomy, CCR7^- CD45RA^- CD8⁺ effector memory T cells were observed in the peritoneal cavity. The frequency of CD4⁺ CD25 ^high T cells in both the peripheral blood and peritoneal cavity was elevated in patients at advanced stage [control vs stage IV in the peripheral blood: 6.89 (3.39-10.4) vs 15.34 (11.37-19.31), P < 0.05, control vs stage IV in the peritoneal cavity: 8.65 (5.28-12.0) vs 19.56 (14.81-24.32), P < 0.05]. On the other hand, the suppression was restored with CD4⁺ CD25^high T cells from their own peripheral blood. This study is the first to analyze lymphocyte and cytokine production in the peritoneal cavity in patients with gastric cancer. Immune regulation at advanced stage is reversible at the point of gastrectomy.

CONCLUSION: The immunological milieu in the peritoneal cavity of patients with advanced gastric cancer elicited a Th2 response even at gastrectomy, but this response was reversible.

• Cytokines
• Gastric cancer
• Lymphocytes
• Peritoneal cavity
• Regulatory T cell

• Aged
• Androgen Antagonists/administration & dosage
• Anilides/administration & dosage
• Anilides/adverse effects
• Antibodies, Monoclonal/administration & dosage
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Disease Progression
• Dose-Response Relationship, Drug
• Humans
• Male
• Middle Aged
• Nitriles/administration & dosage
• Nitriles/adverse effects
• Prostate-Specific Antigen/blood
• Prostate-Specific Antigen/immunology
• Prostatic Neoplasms/blood
• Prostatic Neoplasms/drug therapy
• Prostatic Neoplasms/pathology
• Prostatic Neoplasms/surgery
• Tosyl Compounds/administration & dosage
• Tosyl Compounds/adverse effects
• Treatment Outcome

• P30 CA014520 NCI NIH HHS
• T32 CA009614 NCI NIH HHS
• T32 CA009614-21 NCI NIH HHS
• T32CA009614 NCI NIH HHS

• CD8-Positive T-Lymphocytes/immunology
• Cancer Vaccines/administration & dosage
• Cancer Vaccines/immunology
• Cancer Vaccines/therapeutic use
• Epitopes
• Granulocyte-Macrophage Colony-Stimulating Factor/immunology
• Humans
• Immunization, Secondary
• Melanoma/pathology
• Melanoma/therapy
• Neoplasms/drug therapy
• Neoplasms/immunology
• T-Lymphocytes/immunology
• Vaccination/methods
• Vaccines, Subunit/immunology
• Vaccines, Subunit/therapeutic use

• CA121612 NCI NIH HHS
• R01 CA080964 NCI NIH HHS
• CA123864 NCI NIH HHS
• R01 CA119123 NCI NIH HHS
• CA080964 NCI NIH HHS
• CA141278 NCI NIH HHS
• CA119123-03 NCI NIH HHS

Approximately 50% of human malignancies carry p53 mutations, which makes it a potential antigenic target for cancer immunotherapy. Adoptive transfer with p53-specific cytotoxic T-lymphocytes (CTL) and CD4⁺ T-helper cells eradicates p53-overexpressing tumors in mice. Furthermore, p53 antibodies and p53-specific CTLs can be detected in cancer patients, indicating that p53 is immunogenic. Based on these results, clinical trials were initiated. In this paper, we review immunological and clinical responses observed in cancer patients vaccinated with p53 targeting vaccines. In most trials, p53-specific vaccine-induced immunological responses were observed. Unfortunately, no clinical responses with significant reduction of tumor-burden have occurred. We will elaborate on possible explanations for this lack of clinical effectiveness. In the second part of this paper, we summarize several immunopotentiating combination strategies suitable for clinical use. In our opinion, future p53-vaccine studies should focus on addition of these immunopotentiating regimens to achieve clinically effective therapeutic vaccination strategies for cancer patients.

• vaccination
• aml
• mm
• t cell
• cpg
• wt1

• Adolescent
• Antigens, Neoplasm/chemistry
• Antigens, Neoplasm/immunology
• CD4-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/immunology
• Cancer Vaccines/adverse effects
• Cancer Vaccines/immunology
• Cancer Vaccines/therapeutic use
• Female
• Humans
• Leukemia, Myeloid, Acute/immunology
• Leukemia, Myeloid, Acute/pathology
• Leukemia, Myeloid, Acute/therapy
• Male
• Mannitol/adverse effects
• Mannitol/analogs & derivatives
• Mucin-1/adverse effects
• Mucin-1/chemistry
• Mucin-1/immunology
• Multiple Myeloma/immunology
• Multiple Myeloma/pathology
• Multiple Myeloma/therapy
• Myeloblastin/adverse effects
• Myeloblastin/chemistry
• Myeloblastin/immunology
• Neoplasm Staging
• Neoplasm, Residual/immunology
• Neoplasm, Residual/pathology
• Neoplasm, Residual/therapy
• Oleic Acids/adverse effects
• Oligodeoxyribonucleotides/adverse effects
• Oligodeoxyribonucleotides/immunology
• Peptides/adverse effects
• Peptides/immunology
• Peptides/therapeutic use
• Pilot Projects
• Treatment Outcome
• WT1 Proteins/adverse effects
• WT1 Proteins/chemistry
• WT1 Proteins/immunology

• CA33084 NCI NIH HHS
• CA18029 NCI NIH HHS
• P01 CA018029 NCI NIH HHS
• R37 CA033084 NCI NIH HHS
• R01 CA033084 NCI NIH HHS

• cell intrinsic modulators of metabolism and memory formation
• toll-like receptor agonist
• ctla-4
• pd-1
• wnt/β-catenin
• mtor

• Adjuvants, Immunologic
• Adoptive Transfer
• Antigens, Differentiation, T-Lymphocyte/immunology
• Antigens, Neoplasm/immunology
• Cancer Vaccines/immunology
• Cancer Vaccines/therapeutic use
• Humans
• Immunotherapy
• Neoplasms/immunology
• Neoplasms/therapy
• Randomized Controlled Trials as Topic
• T-Lymphocyte Subsets/immunology
• Toll-Like Receptors/agonists
• Treatment Outcome

• Z99 CA999999 Intramural NIH HHS
• ZIA BC010763 Intramural NIH HHS
• ZIA BC011037 Intramural NIH HHS

• dna vaccine
• prostate cancer
• prostatic acid phosphatase
• clinical trial
• t-cell immune response monitoring

• Acid Phosphatase
• Antigens, Neoplasm/administration & dosage
• Cancer Vaccines
• Cell Proliferation/drug effects
• Cells, Cultured
• HLA-A2 Antigen/metabolism
• Humans
• Immunization, Secondary
• Interferon-gamma/metabolism
• Lymphocyte Activation/drug effects
• Male
• Neoplasm Recurrence, Local
• Prostatic Neoplasms/immunology
• Prostatic Neoplasms/therapy
• Protein Tyrosine Phosphatases/administration & dosage
• T-Lymphocytes, Cytotoxic/immunology
• T-Lymphocytes, Cytotoxic/metabolism
• T-Lymphocytes, Cytotoxic/pathology
• Vaccines, DNA

• K23 RR016489 NCRR NIH HHS
• UL1 RR025011 NCRR NIH HHS
• 1UL1RR025011 NCRR NIH HHS
• K23 RR16489 NCRR NIH HHS

• ctl
• prostatic acid phosphatase (pap)
• hla-a2
• elispot
• epitope

• Acid Phosphatase
• Animals
• Antigens, Neoplasm/genetics
• Antigens, Neoplasm/immunology
• Antigens, Neoplasm/metabolism
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/metabolism
• CD8-Positive T-Lymphocytes/pathology
• Cancer Vaccines
• Clone Cells
• Epitopes, T-Lymphocyte/genetics
• Epitopes, T-Lymphocyte/immunology
• Epitopes, T-Lymphocyte/metabolism
• HLA-A2 Antigen/genetics
• HLA-A2 Antigen/immunology
• HLA-A2 Antigen/metabolism
• Humans
• Immunization
• Interferon-gamma/metabolism
• Lymphocyte Activation
• Male
• Mice
• Mice, Transgenic
• Peptide Fragments/genetics
• Peptide Fragments/immunology
• Peptide Fragments/metabolism
• Prostatic Neoplasms/blood
• Prostatic Neoplasms/immunology
• Prostatic Neoplasms/pathology
• Prostatic Neoplasms/therapy
• Protein Binding
• Protein Tyrosine Phosphatases/genetics
• Protein Tyrosine Phosphatases/immunology
• Protein Tyrosine Phosphatases/metabolism