A recent review series in Blood journal explored research advancements and opportunities in the field of hematologic diseases, focused on the development, scalability and commercialization of cutting-edge immunotherapies.
“It’s incredible to watch the field advance so rapidly, with such dramatic implications for patients,” said Dr. Steven Devine, Medical Director, Be The Match BioTherapies®. “Many of these immunotherapies quite literally change the paradigm for treating diseases of the blood.”
Here’s a look at three of the intriguing research areas highlighted in the review:
Understanding relapse after CAR-T treatment
The two CAR-T therapies approved by the U.S. FDA have proved powerful in many patients with acute lymphoblastic leukemia, yet a significant fraction of patients relapse. In some cases, the new tumors express little or no CD19, the tumor surface molecule targeted by existing CAR-T treatments. In other cases, the tumor cells have a variant of CD19, but without the precise epitope that the treatment is designed to bind with.
Researchers are trying to understand this phenomenon of “tumor escape,” and looking to develop CAR-T therapies that will target multiple tumor surface molecules beyond CD19, to make it harder for malignant cells to evade them. One option may be creating a bispecific or multispecific CAR to bind to epitopes on different molecules.
A new approach to graft-versus-host disease
Graft-versus-host disease (GVHD) is generally treated with pharmacological intervention to suppress the immune system, but a broad suppression of the immune system has clear drawbacks. New understanding of regulatory cells may pave the way for a less toxic approach.
Several sub-classes of regulatory cells could play a role, including regulatory T cells (known as Tregs) and natural or thymic Tregs (nTregs), innate lymphoid cells, myeloid-derived suppressor cells and NK cells.
“At this time, nTreg infusions represent the most promising cellular therapy for preventing and treating GVHD,” write co-authors Bruce Blazar of the University of Minnesota, Kelli MacDonald of the Antigen Presentation and Immunoregulation Laboratory and Geoffrey Hill of the Royal Brisbane and Women’s Hospital in Australia.
Immunotherapy advances may be leading to a breakthrough in cancer vaccines
“The use of whole cell-based strategies such as dendritic cell/tumor fusions have yielded provocative results in single-arm studies and are currently being explored in multicenter randomized trials,” writes David Avigan and Jacalyn Rosenblatt of Harvard Medical School.
The idea behind cancer vaccines is to present the immune system with antigens or neoantigens associated with a patient’s tumor to prod it into moving against those targets. The key is identifying the optimal antigenic targets that will steer the immune system toward the cancer without provoking a broader autoimmune response.
If research comes to fruition, cancer vaccines could become the ultimate personalized therapy, with each dose specially designed to target the specific antigens or neoantigens on a given patient’s tumor.
Taken together, the review series in Blood paints an exciting picture of the future of hematology, thanks to research advancements in both academic and industry labs around the world.