Undisclosed anti PD-1 mAb / Cellectis, MabQuest - LARVOL DELTA

Stromal depletion by TALEN-edited universal hypoimmunogenic FAP-CAR T cells enables infiltration and anti-tumor cytotoxicity of tumor antigen-targeted CAR-T immunotherapy. (PubMed, Front Immunol) - "Combination therapy of FAP UCAR, Meso UCAR T cells and the checkpoint inhibitor anti-PD-1 significantly reduced tumor burden and prolonged mice survival. Our study thus proposes a novel treatment paradigm for successful CAR T-cell immunotherapy against stroma-rich solid tumors."

CAR T-Cell Therapy • IO biomarker • Journal • Stroma • Breast Cancer • Fibrosis • Oncology • Solid Tumor • Triple Negative Breast Cancer • CAFs • FAP • MSLN

Preclinical activity and manufacturing feasibility of genetically modified PDCD-1 knockout (KO) tumor-infiltrating lymphocyte (TIL) cell therapy (AACR 2022) - "Background: Adoptive cell therapy with autologous TIL has demonstrated an objective response rate (ORR) of 36% in the post-immune checkpoint inhibitor (ICI) setting in patients (pts) with advanced/unresectable melanoma (Sarnaik JCO 2021), while in ICI-naïve pts who received early-line combination of TIL and pembrolizumab, the ORR was 60%, with a 30% CR rate (O’Malley SITC 2021). Although effective, anti-PD-1 therapy is limited by poor penetration into the tumor, internalization, and endocytic clearance, in contrast with TIL, which overcome this inherent limitation... Anti-tumor activity of PD-1 KO TIL was superior to mock TIL suggesting that endogenous PD-1 inhibition may confer a functional advantage to the TIL over an antibody combination. PD-1 KO TIL clinical manufacturing was feasible and the TIL product quality attributes and phenotype were acceptable; importantly, lack of complete PD-1 KO may spare other PD-1-dependent in vivo cellular functions. Together,..."

IO biomarker • Preclinical • Melanoma • Oncology • Solid Tumor • PD-1 • PTPRC

Defining Resistance to Treatment with Anti-PD-1/PD-L1 Immunotherapy - "In order to address this unmet need, the Society for Immunotherapy of Cancer (SITC) convened experts from academia, industry, and government to define PD-1/PD-L1 resistance via three categories: primary resistance, secondary resistance, and progression after treatment discontinuation....collectively defined each resistance classification, timeframes that delineate each resistance type, and methods to confirm resistance.....Additional CRI scientists involved in this effort included...Dung T. Le, M.D..."

[VIRTUAL] Genetic modification of Iovance’s TIL through TALEN-mediated knockout of PD-1 as a strategy to empower TIL therapy for cancer (ESMO 2020) - "Consequent TIL killing of cancer cells may be enhanced while avoiding the toxicity associated with systemic anti-PD-1 therapy, thereby consolidating two complementary benefits in one treatment...Legal entity responsible for the study: Iovance Biotherapeutics, Inc. Funding: Iovance Biotherapeutics, Inc."

IO Biomarker • Cervical Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor