MD Anderson Now to Offer Solution for Cellular Therapy Toxicities

Katy Rezvani, MD, PhD

MD Anderson Cancer Center now offers the inducible caspase-9 (CaspaCIDe®) safety switch, related technologies, and rimiducid for use in patients receiving cellular therapies at the cancer center through a license agreement with Bellicum Pharmaceuticals, according to a press release from both organizations.¹

CaspaCIDe safety switch contains a CID-binding domain which is connected to the signaling domain of caspase-9. With an infusion of rimiducid, the caspase-9 domain is activated, causing selective apoptosis of the CaspaCIDe-containing cells. The purpose of this technology to help with the common adverse events (AEs) observed with the use of cellular therapies in patients with cancer, such as cytokine release syndrome (CRS) and neurotoxicity. The technology can also be administered long after the initiation of a cellular therapy.

“The unique inducible caspase-9 technology covered by this agreement has the potential to reduce the risk of serious adverse events associated with cellular therapies and to improve patient outcomes,” said Katy Rezvani, MD, PhD, professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson, in a press release. “We have successfully applied the technology to existing cell therapies, and we look forward to the potential future applications made possible by this agreement.”

Research shows that adoptive cell therapies (ACTs) lead to AEs that are more prevalent than AEs associated with radiation and chemotherapy, and the AEs from cellular therapies can last for several years. CRS, the most common toxicity, is observed with all ACTs and typically manifests as fever and chills to start. Immunosuppressive agents like glucocorticoids and anti-IL-6/IL-6 receptor antibodies are used to treat CRS, however experts still consider this AE to be a challenge in patients with cancer.²

The use of chimeric antigen receptor (CAR) T-cell therapies, T-cell receptor engineering therapies (TCR-T) and tumor-infiltrating lymphocyte (TIL) therapy can cause neurotoxicity, which has clinical characteristics like confusion, delirium, expressive aphasia, obtundation, myoclonus, and seizure. This toxicity can be concurrent with CRS, making for a bigger treatment challenge. Other AEs related to the use of cellular therapies include off-target associated with both CAR T-cell therapy, and high dose IL-2–related toxicity associated with TILs.

In studies, the CaspaCIDe safety switch has demonstrated improvement of symptoms within rimiducid 24 hours. There are 45 clinical trials ongoing at MD Anderson that may be impacted by this license agreement. Currently, MD Anderson is the site for 12 clinical trials of chimeric antigen receptor T-cell therapies, 5 trials of T-cell receptor engineering therapies, 5 studies of tumor-infiltrating lymphocytes, and 23 trial of natural killer cell therapies.¹

“We are excited to expand our CaspaCIDe agreement with MD Anderson to include a broader set of programs to benefit cancer patients,” said Rick Fair, president and CEO of Bellicum Pharmaceuticals, in the press release. “We believe that our switch technology may enhance the benefit/risk profile of cell therapies. We intend to continue to pursue opportunities to expand its use via external collaborations with other leaders in the field.”

_Reference:

_{1. MD Anderson and Bellicum announce additional license agreement for use of CaspaCIDe® safety switch. News release. MD Anderson Cancer Center. September 1, 2021. Accessed September 3, 2021. https://bit.ly/38AgSHs}

_{2. Jin Y, Dong Y, Zhang J, et al. The toxicity of cell therapy: Mechanism, manifestations, and challenges. J Appl Toxicol. 2021;41(5):659-667. doi: 10.1002/jat.4100}