Optimizing Cancer Immunotherapy through Combination Therapies: Advances in Chemoimmunotherapy, Lymphodepletion, and Precision Medicine

Abstract

Chemoimmunotherapy was a challenge issue in an early clinical study. Cytotoxic chemotherapy was immunosuppressive while, in the clinic, chemoimmunotherapy demonstrated supporting immunotherapy. To increase ACT (adoptive cell transfer) immunotherapy and decrease the effects of chemotherapy for Tumor-infiltrating lymphocytes (TILs) to treat solid tumors, we began to study chemoimmunotherapy by isolating and culturing primary tumor cells and immune cells from the removed solid tumor tissues before 1994. After about 30-40 years of efforts, results of optimizing combination treatment have demonstrated that chemotherapy combined with immunotherapy (called chemoimmunotherapy) is better than monotherapy; now there are four fields to be developed for the optimizing combination, including (1) Lymphodepletion (LD) supporting ACT immunotherapy for Advanced Cancer, (2) Chemoimmunotherapy (CI) supporting treatment for Advanced Cancer, (3) Immune Checkpoint Inhibition (ICI) combined with immunotherapy, and (4) Precision Medicine (PM) supporting immunotherapy for Advanced Cancer. Precision therapy can cover all three, as described above, as well as LD, chemoimmunotherapy, and ICI combination. Techniques for precision therapy include tumor tissue biobanks, single cell technique, clinical genomics, and artificial intelligence to support the combination treatment. Overall, the latest generation of optimizing combination therapies is more specific and sensitive in treating neoplastic diseases than older versions with fewer side effects. Based on 30–40 years of R&D to improve immunotherapy for patients with advanced cancer and based on increasing research, it is time to define combinations treatment and evaluate the efficacy of optimizing combination treatments for oncological diseases