Drugs & Updates

BioNTech’s Solid Tumor CAR-T Therapy hits PRIME Time from EU

Jun 23, 2022 11:31pm

For many decades, cancer therapy mainly relied on surgery, chemotherapy, and radiotherapy. In recent years, the concept of stimulating the patient’s immune response and the observed durability of responses has established cancer immunotherapies as a novel treatment option for a series of cancer types.

One promising approach is the adoptive transfer of T cells genetically engineered to express a chimeric antigen receptor (CAR). Such CAR-T cells recognize surface antigens independently from MHC restriction. When targeted to tumor surface antigens, CAR-T cells proliferate and kill tumor cells upon antigen contact.

CARs are composed of an extracellular binding domain, a hinge region, a transmembrane domain, and one or more intracellular signaling domains. Single‐chain variable fragments (scFvs) derived from tumor antigen‐reactive antibodies are commonly used as extracellular binding domains. All CARs harbor the CD3ζ chain domain as the intracellular signaling domain.

Second‐ or third‐generation CARs also contain co‐stimulatory domains, like CD28 and/or 4‐1BB, improving proliferation, cytokine secretion, resistance to apoptosis, and in vivo persistence. Third‐generation CARs exhibit improved effector functions and in vivo persistence as compared to second‐generation CARs. Fourth‐generation CARs, called TRUCKs or armored CARs, combine the expression of a second‐generation CAR with factors that enhance anti‐tumoral activity, such as cytokines, co‐stimulatory ligands, or enzymes that degrade the extracellular matrix of solid tumors.

To enhance the safety of CAR-T cell therapy, so‐called smart T cells which are either equipped with a suicide gene or include synthetic control devices are under non‐clinical and clinical investigation. Thus, CAR-T cells are complex medicinal products with the unique feature of being able to self‐amplify and persist in treated patients. Their translation from basic and pre‐clinical research to clinical trials therefore poses many challenges that slow down clinical development, while many cancer patients desperately await novel treatment options.

Just a couple months after showcasing a small data set, BioNTech’s solid tumor CAR-T cell therapy is ready for prime time. BNT211 has been granted a priority medicines, or PRIME designation from the European Medicines Agency, giving the famed German biotech extra help during the regulatory process. The designation specifically targets third- or later-line treatment of testicular germ cell tumors, which BioNTech Chief Medical Officer and co-founder Özlem Türeci, M.D., said is a population that is associated with poor prognosis and few remaining treatment options.

In April 2022, BioNTech showcased phase 1/2 data from 16 patients with solid tumors that associated BNT211 with a disease control rate of 86% and an overall response rate of 43%. These data, out at the American Association for Cancer Research meeting in New Orleans, were used to support the PRIME designation.

The therapy is an autologous CAR-T cell therapy targeting oncofetal antigen Claudin-6 that is being tested in the phase 1/2 solid tumor trial with or without a CLDN6-encoding CAR-T cell amplifying RNA vaccine called CARVac. “We believe that a combination of engineered T cells and mRNA vaccines in one treatment regimen can stimulate and expand T cells. This could enable us to develop truly powerful precision immunotherapies,” Türeci said.

With the PRIME status in hand, BioNTech can step on the gas to move BNT211 through the clinic. Companies granted this tag are eligible for early support from regulators to speed development of promising medicines and get them to patients faster.




Dr Shilpa Subramanian

Dr. Shilpa Subramanian is a MDS, Periodontist and currently manages Global Pharmacovigilance and Medical Affairs Operations at a Healthcare company in Mumbai. She is passionate about staying ahead of the curve in clinical and non-clinical advances in the field of pharma and healthcare.

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