Mechanisms of and approaches to overcoming resistance to immunotherapy.

Mechanisms of and approaches to overcoming resistance to immunotherapy. Hematology Am Soc Hematol Educ Program. 2019 Dec 06;2019(1):226-232 Authors: Schultz L, Gardner R Abstract Immunotherapies have been successfully developed for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) with FDA approval of blinatumomab, inotuzumab, and tisagenlecleucel for relapsed or refractory patients. These agents target either CD19 or CD22, which are both expressed on the surface of the leukemic blasts in the majority of patients. The use of these agents has greatly transformed the landscape of available treatment, and it has provided curative therapy in some patients. As the field has matured, we are learning that for most patients, the currently available immunotherapies are not curative. Leukemic resistance to both CD19 and CD22 pressure has been described and is a major component of developed resistance to these therapies. Patients with B-ALL have developed CD19- or CD22-negative B-ALL, and in more rare cases, they have undergone lineage switch to acute myeloid leukemia. Current efforts are focusing on overcoming antigen escape, either by forced antigen expression or by dual-targeting therapies. A functional immune system is also required for maximal benefit of immunotherapy, particularly with chimeric antigen receptor (CAR) T-cell therapies. Data are now being produced that may allow for the prospective identification of patients whos...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research