Here, we describe the in-depth characterization of an HLA-A*02:01-presented peptide derived from the cancer germline antigen preferentially expressed antigen in melanoma (PRAME) that opens an avenue of new opportunities for patients with solid cancers which we aim to leverage by two distinct TCR-based therapeutic modalities, TCR-engineered T cells (ACTengine® IMA203) and TCR Bispecifics (TCER® IMA402). Conclusions Here, we demonstrate comprehensive target characterization and validation data supporting the nearly ideal target properties of PRAME that can be exploited for the benefit of patients: PRAME is highly cancer-associated, homogenously expressed, presented at high target density, highly prevalent across many solid cancers and clinically validated, underlining its potential to reach a large cancer patient population. Trial Registration NCT03686124 Ethics Approval The study was approved by the institutional review board/ethics committee as required for each participating site.
2 years ago
Clinical • IO biomarker
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HLA-A (Major Histocompatibility Complex, Class I, A) • PRAME (Preferentially Expressed Antigen In Melanoma)
IMA203 T cells are infused after lymphodepletion with fludarabine, and cyclophosphamide followed by low-dose IL-2. In summary, IMA203 shows a manageable safety profile and, to our knowledge, is the first TCR-T product candidate associated with frequent objective responses across multiple solid tumors at doses below 1 billion transduced T cells. Three expansion cohorts are currently being initiated to further study the safety and anti-tumor activity of IMA203 in solid tumors: IMA203 monotherapy at target dose, combination with a checkpoint inhibitor and a next-gen product candidate IMA203CD8 utilizing IMA203 co-transduced with a CD8 co-receptor.
over 2 years ago
Clinical • Clinical data • P1 data
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CD8 (cluster of differentiation 8) • HLA-A (Major Histocompatibility Complex, Class I, A) • PRAME (Preferentially Expressed Antigen In Melanoma)
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HLA-A*02
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cyclophosphamide • fludarabine IV • IMA203 • IMA203CD8
Here, we show preclinical data from our next-generation product candidate IMA203CD8 utilizing the IMA203 TCR co-transduced with a CD8 co-receptor. The differential functional profiles of TCR-T cells co-expressing different types of CD8 constructs suggests that optimizing the type of co-receptor is relevant to maximize anti-tumor response and reveals CD8αβ to be the optimal co-receptor for the IMA203 PRAME TCR. Harnessing the anti-tumor potency of CD4 T cells may enhance depth and durability of anti-tumor responses and potentially improve the clinical outcome of TCR-T in patients with solid cancer.
over 2 years ago
Preclinical
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CD8 (cluster of differentiation 8) • HLA-A (Major Histocompatibility Complex, Class I, A) • CD4 (CD4 Molecule) • PRAME (Preferentially Expressed Antigen In Melanoma)
After lymphodepletion with fludarabine and cyclophosphamide, T cells are infused, followed by low-dose IL-2. The next step is to assess response rates at higher dose levels and durability of responses. Trial Registration NCT03686124
3 years ago
Clinical • Late-breaking abstract
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CD8 (cluster of differentiation 8) • HLA-A (Major Histocompatibility Complex, Class I, A) • PRAME (Preferentially Expressed Antigen In Melanoma)
Safety, biological activity and anti-tumoral efficacy are closely monitored throughout and following lymphodepletion with Fludarabine and Cyclophosphamide, T cell infusion and low dose IL-2 treatment. Taken together, treatment-emergent adverse events for ACTengine® product candidates were transient and manageable and in line with published data for autologous cell therapy in solid cancers. First anti-tumor activity in heavily pre-treated patients after infusion of low cell doses was unexpected, and together with robust biological activity warrants exploration of IMA201, IMA202 and IMA203 product candidates at target dose.
over 3 years ago
Tumor Mutational Burden • IO biomarker
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TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • MAGEA4 (Melanoma antigen family A, 4) • PRAME (Preferentially Expressed Antigen In Melanoma) • MAGEA1 (MAGE Family Member A1)