Tucaresol-Cyclophosphamide Combination Therapy: Proposal for a Safe, Affordable Alternative to CAR T-Cell Therapy

Abstract

Christopher L. Penney, Boulos Zacharie and Jean-Simon Duceppe

Chimeric Antigen Receptor (CAR) T-cell therapy is a newer immunotherapeutic process in which genetic engineering is used to incorporate a receptor protein into a patient’s T-cells thereby permitting the modified T-cells to recognize and eradicate tumors. Initially, CAR T-cell therapy was reserved as a last resort when standard cancer treatments failed to provide significant efficacy but subsequently, CAR T-cell therapy is finding use against earlier stage cancers. Since 2017, seven CAR T-cell therapies have attained FDA approval for treatment of hematological cancers. The latest approval, November 8, 2024, is for treatment of B-cell acute lymphoblastic leukemia. However, CAR T-cell therapy does not always provide a lasting anticancer response which leads to loss of tumor remission. The percent loss of tumor remission depends upon the type of hematological cancer being treated. Although currently limited to hematological cancers, CAR T-cell therapy provides cancer patients a significant increase in survival unattainable with traditional cancer treatment regimens. However, two significant issues accompany CAR T-cell therapy. The first is multiple toxicity issues which although occurring individually in a low percentage of patients, taken together constitute a significant probability of encountering a potentially fatal side effect. The second problem is the high cost of CAR T-cell therapy starting at $450,000 US per treatment. Contributing to both of these problems is the fact that CAR T-cell therapy is labor intensive which will exacerbate existing clinical facilities already challenged by a myriad of mutating pathogens and an aging population. Against this setting is proposed therapy consisting of clinical stage and FDA approved anticancer drugs with excellent safety records. Proposed herein is combination therapy with Tucaresol, up-regulates CD4+ and CD8+ T-cells, and cyclophosphamide, down-regulates Treg cells, as a convenient, cost effective cancer treatment.

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