In multiple myeloma, CS1 is considered a well-defined antigen, which investigators already are targeting with CAR-T therapy, according to Dr Munshi. “But this group put it together with NKG2D, an interesting molecule, which is scientifically intriguing,” he says. “They showed a good response.”

Nevertheless, for this and other bispecific antibodies to work best in patients, Dr Munshi said there is a prerequisite: a functional immune system must be present. CAR-T therapy has a clear advantage over bispecific antibodies right now, he explained, because “you can overcome some of the immune-suppressive environment” that occurs. Still, given the prohibitive costs of CAR-T’s customized approach, Dr Munshi and others believe bispecific antibodies could provide an economical alternative for patients in the future, broadening access to treatment.

Michael Verneris, MD, director of bone marrow transplant and cellular therapy at Children’s Hospital in Denver, Colorado, also sees an evolving role for these next-generation designer antibodies. Although the need for intact immunity and a lack of persistent therapeutic effect pose barriers right now, he says, bispecific antibodies have considerable upside, as well.


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“These are modular, relatively small molecules that can be quick to produce,” he said. “If ‘A’ and ‘B’ don’t work, you can keep on mixing and matching until you can create whatever you want.” One obvious advantage to patients is that if complications arise, they can be addressed quickly, he said.

“The great hope is that these will be in the deck of options for patients,” as an integral part of a multipronged strategy against cancer, Dr Verneris said.

Although no bispecific monoclonal antibodies in the first-line setting exist yet, he is confident that clinical trials in patients with early-stage cancers eventually will take place, when chemotherapy damage to their immune systems is not so extensive.

Dr Verneris said he has watched unlikely strategies in immuno-oncology gradually unfold successfully before, and the same could happen with bispecific antibodies. “It’s been hugely gratifying to see some of these ideas come raging forward.”

References

  1. Krishnamurthy A, Jimeno A. Bispecific antibodies for cancer therapy: a review. Pharmacol Ther. 2018;185:122-134.
  2. FDA grants regular approval to blinatumomab and expands indication to include Philadelphia chromosome positive B-cell. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm566708.html. Updated July 12, 2017. Accessed August 20, 2018.
  3. Chan, WK, Kang S, Youssef Y, et al. A CS1-NKG2D bispecific antibody collectively activates cytolytic immune cells against multiple myeloma. Cancer Immunol Res. 2018;6(7):776-787.