Cancer immune therapy for lymphoid malignancies: recent advances

Uffe Klausen, Nicolai Grønne Dahlager Jørgensen, Jacob Handlos Grauslund, Morten Orebo Holmström, Mads Hald Andersen

Immunotherapy has played an important part in improving the life of patients with lymphoproliferative diseases especially since the addition of rituximab to chemotherapy in the CD20-positive neoplasms in the 1990s. While this field of passive immunotherapy is continuously evolving, several breakthroughs will expand the treatment modalities to include more active immunotherapy. With the approval of immune checkpoint-blocking antibodies for Hodgkin lymphoma and bispecific antibodies for acute lymphoblastic leukemia (ALL), activation of endogenous T cells already plays a role in several lymphoid malignancies. With the approval of cellular therapies with CAR-T cells for ALL and diffuse large B cell lymphoma, the impact of the manipulation of immune responses is taken even further. Vaccines are cellular therapies in the opposite end of the spectrum in terms of side effects, and while the big breakthrough is still to come, the prospect of a very low-toxic immunotherapy which could be applicable also in premalignant states or in frail patients drives a considerable research activity in the area. In this review, we summarize the mechanisms of action and clinical data on trials in the lymphoid neoplasms with chimeric antigen receptor T cells, bispecific antibodies, immune checkpoint-blocking antibodies, and antineoplastic vaccination therapy.