Last year Dr Brian Koffman healthunlocked.com/user/bko... wrote a succinct piece Bispecific Antibodies: what are they and are they the future of treatment for CLL (chronic lymphocytic leukemia)? cllsociety.org/2020/06/bisp...
"So along comes the bispecific antibody, or BsAb. These clever man-made antibodies, as the name suggests, exploit the Y shape of the antibodies. The assemblage has two different antibodies with two different targets, one found on the cancer cell and the other, typically CD3, a surface marker found on those lazy T cells. This combo links the two cells in a communal death hug for the cancer cell as it makes it easy for even an exhausted T cell to do its duty. It’s like hitting 2 birds with 1 stone"...
..."BsAb therapy is different than CAR-T as it isn’t a cellular therapy, but “humoral”, using an intravenous liquid approach to push the immune system and lazy T cells back into action. Since it’s “off the shelf” and not specific to each patient, it has potential advantages over CAR-T in treating blood cancers.
I say potential, as there are no bispecific antibodies approved or even being actively developed in CLL, but as their efficacy in related B cell lymphomas is increasingly demonstrated, more CLL trials are sure to come".
One such clinical trial (phase 1/ 2) is still recruiting patients including CLL clinicaltrials.gov/ct2/show... Though this trial is probably not relevant to most, it could be of particular interest to patients encountering resistance to a BTK inhibitor. That's based on pre-clinical studies showing synergy between BTKis and bispecific antibodies. vjhemonc.com/video/z9erpexg...
"What we were really intrigued by is when we took samples from patients with ongoing treatment with a BTK inhibitor, we saw more rapid killing and more complete killing of the CLL cells. So, it looked like that the patient who were on BTK inhibitor treatment improved the ability of the T-cells to kill the CLL cells".
"So, right now we have- this is a preclinical molecule, so there’s no plan to really bring this to the clinic. But antibodies, bispecific antibodies with similar designs are quite advanced in studies for diffuse large B-cell lymphoma, for some of the more aggressive lymphoma subtypes. These are typically antibodies that target CD20 instead of the CD90 that we use in our preclinical model. So, CD20-CD3 bispecific antibodies, and there’s- I presented some data from epcoritamab. That’s the CD20-CD3 bispecific from Genmab. But similar data has also been presented at the ASH meeting a couple years ago from the genetic antibody mosunetuzumab. And these antibodies are now entering clinical trials for CLL patients. And I think that offers really an exciting opportunity to deepen responses, combine these agents with BTK inhibitors".
"And maybe as an important add-on we’ve also seen in our preclinical data that the bispecific antibody was still very efficacious in PBMCs from patients who had started to develop resistance to BTK inhibitors and were progressing on the BTK inhibitor. And I was observed, both in vitro, but then importantly, also in patient-derived xenografts, where we took the samples from these patients who progress on BTK inhibitors, transfer them into NSG mice and treat them with the bispecific antibody. And we saw still very good efficacy against ibrutinib-resistant CLL. So, really an exciting opportunity to bring these novel concepts into the clinic".
See also vjhemonc.com/video/tsai_vsw...
Antibodies after third or fourth covid vaccine
CLL SOCIETY'S ASH POSTER on our Free second opinion program plus two important papers from ASCO
How do I safely live my life with CLL if my antibody test results are one of three scenarios?
