CAR-Tnm cell therapy for melanoma targeting TYRP-1
Grant Award Details
Grant Type:
Grant Number:
TRAN1-12258
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$5,904,462
Status:
Active
Grant Application Details
Application Title:
CAR-Tnm cell therapy for melanoma targeting TYRP-1
Public Abstract:
Translational Candidate
Autologous naive/memory progenitor T cells genetically modified to express a chimeric antigen receptor targeting the Tyrosinase-related protein 1
Area of Impact
Patient with melanoma, without response or with relapse after immune checkpoint blockade therapy and patients with rare melanoma subtypes.
Mechanism of Action
T cells genetically modified to express the 20D7SL CAR detect and kill melanoma cells with high expression of TYRP-1 (representing ~30% of all melanoma lesions). Our Therapeutic Candidate uses a subset of naïve/memory progenitor T cells (Tnm) with improved ability to engraft and reconstitute a functional memory response compared to fully differentiated T cells. We anticipate that using Tnm cells will lead to a potent and persistent antitumor response.
Unmet Medical Need
Immune Checkpoint Blockade (ICB)-resistant melanoma is an unmet medical need. Despite the success of ICB therapy, 40% of patients with melanoma do not respond, and some responders develop acquired resistance. ICB-resistant melanoma frequency is higher in patients with rare subtypes of melanoma.
Project Objective
Pre-IND meeting
Major Proposed Activities
Autologous naive/memory progenitor T cells genetically modified to express a chimeric antigen receptor targeting the Tyrosinase-related protein 1
Area of Impact
Patient with melanoma, without response or with relapse after immune checkpoint blockade therapy and patients with rare melanoma subtypes.
Mechanism of Action
T cells genetically modified to express the 20D7SL CAR detect and kill melanoma cells with high expression of TYRP-1 (representing ~30% of all melanoma lesions). Our Therapeutic Candidate uses a subset of naïve/memory progenitor T cells (Tnm) with improved ability to engraft and reconstitute a functional memory response compared to fully differentiated T cells. We anticipate that using Tnm cells will lead to a potent and persistent antitumor response.
Unmet Medical Need
Immune Checkpoint Blockade (ICB)-resistant melanoma is an unmet medical need. Despite the success of ICB therapy, 40% of patients with melanoma do not respond, and some responders develop acquired resistance. ICB-resistant melanoma frequency is higher in patients with rare subtypes of melanoma.
Project Objective
Pre-IND meeting
Major Proposed Activities
- Optimize, implement, and validate the Therapeutic Candidate large-scale, GMP-compliant manufacturing and lot release criteria protocols
- Assess safety (selectivity, reactivity in normal tissues, toxicology) and antitumor efficacy (cytotoxicity, cytokine release, tumor growth control).
- Assess feasibility of enrolling patients with rare subtypes of melanoma in the clinical trial, draft clinical protocol and complete pre-IND meeting
Statement of Benefit to California:
In 2021, 11,450 Californians will be diagnosed with melanoma. Around 30% of all cases (3435) will present high levels of TYRP-1 and could potentially benefit from our Therapeutic Candidate. Acral and mucosal melanoma are subtypes of melanoma with higher expression of TYRP-1 and a much lower survival rate than cutaneous melanoma. Their incidence is higher in the Hispanic, Black, and Asian/Pacific Islander populations. This is especially relevant in California, given the diversity of our patients.
Publications
- Nat Commun (2024): CAR-T cell therapy targeting surface expression of TYRP1 to treat cutaneous and rare melanoma subtypes. (PubMed: 38336975)
