Solid hopes for T cell bispecifics

Will next-generation T cell bispecifics find their place in solid tumors?

As next-generation T cell bispecifics hit the clinic, demonstrating efficacy in solid tumors could earn them a place in the immuno-oncology tool kit alongside CAR T cells and checkpoint inhibitors.

T cell bispecific antibodies bring activated T cells into proximity with tumor cells to facilitate tumor killing, similar to the way CARs mobilize T cells to fight cancers. First-generation platforms have a CD3-binding domain linked to a tumor antigen-binding domain; next-generation platforms add a third domain to promote protein stability.

First-generation products Blincyto blinatumomab from Amgen Inc. and Removab catumaxomab from Trion Pharma GmbH have gotten off to a slow start, or have not lived up to expectations. Removab, which was approved for malignant ascites in 2009, was withdrawn from the U.S. market in 2013 and Europe in 2017 because it was not commercially viable.

Blincyto was approved for CD19-positive acute lymphoblastic leukemia (ALL) in 2014, and its label was expanded last month to include patients in remission with minimal residual disease (MRD).

Its sales are growing quickly but remain modest. Revenues for 2017 were $175 million, a 52% increase over 2016.

Developers of next-generation T cell bispecifics have made modifications to improve PK profiles and dosing, and have additional reasons to be optimistic about their place in the immunotherapy landscape.

For instance, preclinical studies suggest T cell bispecifics may penetrate solid tumors better than cell therapies and turn cold tumors hot, making them suitable for combinations with checkpoint inhibitors. And unlike most CAR Ts, which are autologous and must be manufactured to order for each patient, T cell bispecifics are off-the-shelf therapies that can be administered to any patient on demand.

According to BioCentury’s BCIQ database, at least 27 next-generation T cell bispecifics are in the clinic for cancer.


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