Bispecifics emerging as alternative cancer immunotherapy to CAR-T
- Next-gen cancer therapies using reprogrammed T-cells to kill cancers have shown a great deal of promising, boosting the fortunes of developers like Kite Pharma and Juno Therapeutics. But, pharma giant Roche is eyeing another type of cancer therapy using so-called bispecifics, which may avoid some of the manufacturing headaches and severe adverse reactions associated with CAR-T, according to Bloomberg.
- Bispecifics are treatments connecting tumor surface proteins with immune cells. Once connected, the immune cells kill the cancer cells. Unlike CAR-T, there is no need to extract T-cells, reprogram them, and then reintroduced them to the body.
- Due to the challenges associated with CAR-T, the treatment is lengthy and extremely costly. The autologous approach of extracting the patient's own T-cells for re-engineering means each treatment has to be individualized.
The strong enthusiasm around CAR-T has been driven by encouraging data from several small trials. Early studies at the University of Pennsylvania treating children with acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) saw extremely high response rates. For example, in one study of 39 children with ALL treated with CTL019, 92% experienced complete remission, with 70% of the responders still in remission six months later and 75% of patients still alive.
However, there is not yet an approved CAR-T therapy and many challenges remain. Beyond that, the growing field of other cancer immunotherapies has shown promise both as monotherapy and in combinations (think Bristol-Myers Squibb's anti-PD1 Opdivo or Merck's Keytruda).
Bispecifics are yet another approach being taken, with Roche and Amgen in the lead. Amgen already has an approved bispecific, Blincyto, for the treatment of patients with B-cell acute lymphoblastic leukemia (B-cell ALL).
Bispecifics have their own challenges as they are often comprised of fragile combinations of molecules. Amgen's Blincyto only lasts several hours in the human body, therefore requiring a continuous-infusion process, as Bloomberg notes.
While bispecifics have their own associated adverse events, treatment has resulted in a lower rate of the potentially fatal cytokine release syndrome (CRS) seen in CAR-T. CRS occurs when the body's immune system goes into over-drive, which has proved fatal in some cases.
On the upside, however, the manufacturing process (beyond the drug itself) does not require the complex process needed by Kite, Juno, and Novartis to produce their individualized CAR-T therapies.