R01CA266874

A Phase 1 study to evaluate chimeric antigen receptor (CAR) T cells targeting TAG72 in patients with recurrent epithelial ovarian cancer - project summary.

Patients with recurrent epithelial ovarian cancer (EOC) have a poor prognosis with a post-relapse median survival of approximately 30 months and limited therapeutic options, thus presenting a fundamental unmet medical need.

Progress in immunotherapy across a broad range of tumor types provides hope that immunological approaches may improve outcomes for patients with EOC. Particularly, a type of immunotherapy called chimeric antigen receptor (CAR) T cell therapy retrains the immune system to target cancers by recognizing specific cancer markers.

EOC presents several challenges to effective CAR T cell immunotherapy, including poor tumor site infiltration, activation, inadequate function, and persistence of these T cells within the harsh peritoneal tumor microenvironment. Additionally, there is a lack of effective CAR T cell targets on the surface of advanced EOC tumor cells.

Our goal is to develop effective therapies against metastatic EOC, with a specific focus on regional delivery of CAR T cell therapies to treat peritoneal metastasis. TAG72 is highly over-expressed in EOC and other solid tumors with little or no expression in normal tissues, making it an ideal target for CAR T cell therapy.

Our team at City of Hope has developed and completed laboratory testing of a TAG72-targeting CAR T cell therapy. Our preclinical data also supports superior anti-tumor activity when TAG72 CAR T cells are administered regionally by intraperitoneal delivery versus systemically by intravenous delivery, likely due to direct and immediate antigen CAR T cell access to tumor cells.

The hypothesis is that regionally-administered TAG72-CAR T cells will be safe and mediate anti-tumor effects, which will be assessed in the following specific aims:

1) Evaluate safety and feasibility of regional intraperitoneal delivery of TAG72-CAR T cells in patients with advanced EOC in a Phase 1 clinical trial;
2) Assess CAR T cell-mediated immune landscape changes that may indicate therapeutic response or resistance; and
3) Investigate pathways of tumor resistance and CAR T cell-induced tumor evolution.

Our program has incorporated an innovative use of pre-conditioning regimens to our solid tumor CAR T cell therapies, regional routes of CAR T cell administration, and a fully-optimized TAG72-CAR construct. These features aim to improve the potency and selectivity of targeting TAG72+ tumors while potentially minimizing immune responses that limit persistence and/or function of TAG72-CAR T cells.

This approach is significant in that it will expand our therapeutic portfolio for EOC and other solid tumors.

Beckman Research Institute Of The City Of Hope

NOT APPLICABLE

93.395 - Cancer Treatment Research

National Cancer Institute (NCI) [HHS - NIH]

Duarte, California 910103012 United States

Single Zip Code

National Cancer Institute's Investigator-Initiated Early Phase Clinical Trials for Cancer Treatment and Diagnosis (R01 Clinical Trial Required) (PAR-21-033)

Amendment Since initial award the total obligations have increased 383% from $723,036 to $3,489,897.