Stand Up To Cancer is helping scientists make progress in one of the most important areas of cancer research today: expanding the use of autologous CAR T-cell immunotherapy beyond leukemia and other blood cancers to solid tumors, such as osteosarcoma and mesothelioma.
The research could pave the way for a dramatic expansion of a therapy that has revolutionized treatment of blood malignancies but thus far, has had little impact on the solid tumors that make up most cancer cases.
Difficulties in applying the therapy to solid tumors have included the identification of antigens that will serve as targets for the CAR T-cells; getting the cells to the tumors, to stay there to attack the cancerous cells, and dealing with the immunosuppressive environment of the tumor.
Two clinical trials supported by SU2C illustrate the promise of CAR T-cell therapy in solid tumors and were featured at a press conference today at the Annual Meeting 2019 of the American Association of Cancer Research, which is also SU2C’s Scientific Partner. They are:
“A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T-cells: Safety and efficacy.”
Prasad Adusumilli, first author, and Michel Sadelain, senior author, both of Memorial Sloan Kettering Cancer Center. The study was supported in part by the SU2C-Cancer Research Institute Cancer Immunology Dream Team.
“In this phase I clinical trial, intrapleurally administered MSLN-targeted CAR T-cells had no evidence of ‘on-target, off-tumor’ or therapy related toxicity, and there was evidence of CAR T-cell antitumor activity,” the authors reported. “MSLN-targeted CAR T-cell therapy combined with anti-PD1 agents shows encouraging clinical outcomes, thus a combination therapy trial is planned to recruit patients in the second quarter of 2019.
“Administration of HER2-CAR T-cells after lymphodepletion safely improves T cell expansion and induces clinical responses in patients with advanced sarcomas.”
The trial was supported by the St. Baldrick’s Foundation-SU2C Pediatric Cancer Dream Team, among others. Shoba Navai of Baylor College of Medicine is first author. Also, at Baylor are Meenakshi Hegde, senior author; a young investigator on the Dream Team and a 2017 SU2C Innovative Research Grant recipient, and Nabil Ahmed, principal investigator on the trial and a principal investigator on the Dream Team.
The authors concluded: “Administration of lymphodepletion chemotherapy followed by autologous HER2-CAR T-cells is safely tolerated and is associated with objective clinical benefit in some patients with advanced HER2+ sarcoma. Immune correlative studies suggest that the HER2-CAR T-cells given in combination with Flu/Cy lymphodepletion induce endogenous immune reactivity. These findings warrant further evaluation in a phase II study as a single agent or in combination with other approaches.”
