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Principal Investigator: Alexandra P Ikeguchi
Organization: UNIVERSITY OF TX MD ANDERSON CAN CTR
Fiscal Year: 2024
Award: $218,011
Funding agency: National Cancer Institute
Adoptive cellular therapy and therapeutic cancer vaccines have shown promise in solid tumor malignancies but
responses have generally been modest. By combining these two modalities in a rationally designed first-in-
human study, we propose to treat patients with a highly-defined T cell product (comprised of PRAME-specific
memory T cells) in combination with an antigen- specific vaccine (comprised of a curated cocktail of synthetic
long peptides) to augment and sustain the in vivo persistence of transferred PRAME-specific T cells. Addition
of an immune checkpoint inhibitor, (anti-CTLA4), further favorably modulates the tumor environment by
enabling un-fettered CD28 engagement of B7 (to expand the in vivo population of CD28-hi PRAME-specific
memory T cells), lowering the threshold of activation of endogenous tumor-reactive T cells (facilitating antigen-
spreading), and modulating inhibitory activity (by engaging CTLA4+ regulatory cells). This study, as proof of
concept for this triple T cell-based strategy, will be used to address a critical unmet need for patients with
metastatic uveal melanoma, and establish a versatile platform for targeting a broader range of tumor antigens
and tumor types. In this study, all 3 modalities (PRAME vaccine, ETC therapy and anti-CTLA), are reduced to
clinical practice and by using a highly-defined antigen-specific T cell population for adoptive therapy, allows for
rigorous immunologic analysis so that reasons for success or failure can be elucidated.
In an effort to enhance efficacy as well as broaden this approach to benefit a larger pool of patients, PRAME
epitopes presented by additional HLA Class I and II alleles will be identified. The results of the proposed
studies may lead to formal Phase II trials to assess true efficacy, development of a new treatment standard for
refractory metastatic uveal melanoma, and refinement of CD4 T cell and combined CD4 and CD8 T cell
strategies that can be incorporated into future clinical studies.
This proposal leverages the clinically-tested expertise in therapeutic cancer vaccines at ISA Pharma and the
pioneering development of ETC therapy in the Yee Lab to explore an opportunity that is timely and ideally
suited for an academic – industrial partnership.
Terms: <21+ years old><Address><Adoptive Cell Transfers><Adoptive Transfer><Adult><Adult Human><Alleles><Allelomorphs><Antigenic Determinants><Antigens><Antineoplastic Vaccine><Binding Determinants><CD152><CD152 Antigen><CD152 Gene><CD28><CD28 gene><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CTLA 4><CTLA-4 Gene><CTLA-4 blockade><CTLA4><CTLA4 blockade><CTLA4 gene><CTLA4-TM><Cancer Center><Cancer Vaccines><Cancers><Cell Body><Cell Therapy><Cell-Mediated Lympholytic Cells><Cells><Checkpoint inhibitor><Clinical><Clinical Research><Clinical Study><Clinical Trials><Co-Stimulator><Costimulator><Cutaneous Melanoma><Cytolytic T-Cell><Cytotoxic T Cell><Cytotoxic T-Lymphocyte Protein 4><Cytotoxic T-Lymphocyte-Associated Antigen 4><Cytotoxic T-Lymphocyte-Associated Protein 4><Cytotoxic T-Lymphocyte-Associated Serine Esterase-4><Cytotoxic T-Lymphocytes><Development><Disease><Disorder><Distant><Dose><Environment><Epidermal Thymocyte Activating Factor><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Epitope spreading><Epitopes><Event><Eye><Eyeball><Failure><Frequencies><Future><Genetic><Genetic Alteration><Genetic Change><Genetic defect><IL-2><IL2 Protein><Immune checkpoint inhibitor><Immune mediated therapy><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologically Directed Therapy><Immunologics><Immunotherapy><In Vitro><Infusion><Infusion procedures><Interleukin 2><Interleukin 2 Precursor><Interleukin II><Interleukin-2><Interleukine 2><Interleukine 2 Precursor><Interleukine II><Intraocular Melanoma><Liver><Lymphocyte Mitogenic Factor><Malignant Cutaneous Melanoma><Malignant Melanoma of Skin><Malignant Neoplasms><Malignant Tumor><Melanoma Skin><Melanoma Vaccine><Memory><Metastasis><Metastasize><Metastatic Lesion><Metastatic Mass><Metastatic Neoplasm><Metastatic Tumor><Mitogenic Factor><Modality><Modification><Mutation><Neoplasm Metastasis><Neoplasm Vaccines><PRAME><Patients><Peptides><Phase><Population><Process><Refractory><Regimen><Safety><Secondary Neoplasm><Secondary Tumor><Series><Solid Neoplasm><Solid Tumor><Source><Specificity><Surface><T cell based therapeutics><T cell based therapy><T cell directed therapies><T cell growth factor><T cell response><T cell targeted therapeutics><T cell therapy><T memory cell><T-Cell Growth Factor><T-Cell Stimulating Factor><T-Cells><T-Lymphocyte><T-cell therapeutics><T-cell transfer therapy><T4 Cells><T4 Lymphocytes><T44><T8 Cells><T8 Lymphocytes><Testicles><Testing><Testis><Therapeutic><Thymocyte Stimulating Factor><Time><Tumor Antigens><Tumor Vaccines><Tumor-Associated Antigen><Tumor-Infiltrating Lymphocytes><Uveal Melanoma><Vaccination><Vaccines><aCTLA-4><aCTLA4><adoptive T cell transfer><adoptive T-cell therapy><adoptive cell therapy><adoptive cellular therapy><adulthood><anti-CTLA-4><anti-CTLA4><anti-tumor vaccine><antigen spreading><antigen-specific T cells><cancer antigens><cancer infiltrating T cells><cancer metastasis><cell mediated therapies><cell type><cell-based therapeutic><cell-based therapy><cellular therapeutic><cellular therapy><check point blockade><check point immunotherapy><check point inhibitor therapy><check point inhibitory therapy><check point therapy><checkpoint blockade><checkpoint immunotherapy><checkpoint inhibitor therapy><checkpoint inhibitory therapy><checkpoint therapy><chimeric antigen receptor><clinical efficacy><clinical practice><cohort><conditioning><conventional therapy><conventional treatment><cytotoxic CD8 T cells><cytotoxic CD8 T lymphocyte><cytotoxic T-lymphocyte antigen 4><dermal melanoma><developmental><effective therapy><effective treatment><epigenetically><first in man><first-in-human><genome mutation><hepatic body system><hepatic organ system><human study><immune check point blockade><immune check point inhibitor><immune check point therapy><immune checkpoint blockade><immune checkpoint therapy><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><immunogen><immunogenic><in vivo><industrial partnership><industry partner><industry partnership><infusions><killer T cell><kinase inhibitor><malignancy><memory T lymphocyte><neoplasm/cancer><novel><objective response rate><peripheral blood><phase 2 trial><phase II trial><preferentially expressed antigen in melanoma><rational design><response><standard care><standard treatment><success><therapeutic T-cell platform><thymus derived lymphocyte><tumor><tumor cell metastasis><tumor infiltrating T cells><tumor-specific antigen><uvea melanoma><vaccine for cancer><α-CTLA-4><α-CTLA4><αCTLA-4><αCTLA4>