A collaborative research effort on the part of 3 top-tier pharmaceutical companies cite using HemaCare sourced healthy donor PBMCs for their work on developing an allogeneic CAR T cell therapy.  CAR T therapies are among the most promising new cancer treatments approved by the FDA. These therapies have had remarkable success rates in people suffering from aggressive leukemia and lymphoma, who would otherwise be left without treatment options. The number of people who can be treated with this type of therapy is limited, however. CAR T treatment is an autologous therapy, relying on collecting and modifying a patient’s own T cells to fight their disease. Since cancer patients often suffer from a compromised immune system, it’s quite difficult to collect enough healthy T cells for treatment. Several research groups have been looking for a way to make an allogeneic CAR T cell treatment, in which T cells can be sourced from healthy donors.
The authors realized that to produce an allogeneic CAR T cell treatment, they would have to find some way to reduce the risk of graft-versus-host disease (GvHD), a serious complication in which the transplanted donor immune cells attack their host. With this goal in mind, they set out to design a CAR T cell that incorporated a number of different properties to improve both safety and efficacy. To carry out their work, the researchers obtained cryopreserved healthy donor-derived peripheral blood mononuclear cells (PBMC) from HemaCare. HemaCare’s cryopreservation protocols are specifically designed to maintain optimal cell viability and functionality.
After isolating healthy T cells, the authors used gene-editing technology to confer some carefully designed changes:
- B cell maturation antigen (BCMA) targeting the ability to detect and attack cancerous B cells
- Lymphodepletion resistance to promote CAR T cell survival during patient cancer treatment and reduce GvHD potential
- Rituximab-induced CAR T off-switch protects patients from cytokine release syndrome (CRS), while retaining anti-tumor activity
To assess whether the newly designed CAR T cells would work as designed, the scientists tested them in both a cell culture model and a mouse model. The BCMA-targeting CAR T cells demonstrated little to no activity against cell lines without BCMA, but robust cytotoxic activity against BCMA-expressing cancer cells. When the healthy donor-derived CAR Ts were introduced into mice, they exhibited potent and long-lasting anti-tumor activity, though the authors did note that there were some efficacy differences between CAR T cells prepared from different donors.
The off-switch incorporated into the CAR T cells as a safety measure was also highly effective. Peripheral blood examination of CAR T treated mice showed a direct correlation between rituximab administration and the absence of circulating CAR Ts. Pretreating mice with a lymphodepletion agent reduced the potential of GvHD while facilitating CAR T function.
While all of these results are very promising, the BCMA-CAR T cell candidates will have to be tested in clinical trials before scientists can draw any conclusions. Nevertheless, this research is a very encouraging step forward towards the possibility of using healthy donors for CAR T therapy, and the promise of an off-the-shelf cancer treatment.
- Sommer C., et al. Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma. Molecular Therapy. 27 (6) June 2019.