UCLA researchers in the Departments of Microbiology, Immunology, and Molecular Genetics have identified a pre-conditioning reagent for Adoptive Cell Transfer (ACT). The identified reagent specifically ablates T-cells making room for infused cells to engraft and has negligible toxicities compared to traditional conditioning therapies that affect all blood cell types. The identified conditioning process could present a pathway to make ACT more clinically safe.
BACKGROUND:
Advances in the field of immune oncology have transformed the patient care, prolonging the survival of patients with rapidly progressing fatal cancers. In comparison to conventional treatments of cancer (e.g., small molecule chemotherapeutics or surgical intervention), immunotherapeutic approaches pose the least number of adverse side-effects. One form of immunotherapy, ACT, utilizes the patient’s immune system to selectively target and ablate cancer cells. For this, patient’s own tumor infiltrating lymphocytes (TILs) are harvested and expanded ex vivo for reinfusion. ACT has been demonstrated to be the most effective immunotherapy method for cancer treatment with promising clinical results. While much attention has been devoted to making ACT therapies more selective for tumor cells, reducing the immune responses to the reinfused lymphocytes remains a major challenge. Currently, to prevent rejection of reinfused lymphocytes patient’s the immune system is suppressed using chemotherapeutics such as cyclophosphamide. Unfortunately, an associated limitation to this transplant strategy is the identification of effective immune conditioning agents that are non-toxic: noting that many conditioning agents affect multiple blood cell types. Therefore, a current unmet need exists for the identification of an effective pre-conditioning reagent that causes minimal toxicity prior to ACT.
INNOVATION:
UCLA researchers in the Departments of Microbiology, Immunology, and Molecular Genetics have identified an immune-conditioning reagent that specifically ablates T-cells that otherwise reduce the graft potential of ACT. The procedure overcomes toxicities associated with traditional conditioning therapies that affect blood cells. The identified conditioning process could present a pathway to make ACT more clinically relevant. The researchers tested the utility of the conditioning reagent as a means to condition murine models for subsequent transplant with T cells modified with chimeric antigen receptors (CARs). This conditioning process was further demonstrated in non-human primate (NHP) models. Therefore, the proposed conditioning process represents a new method for ACT with minimal toxicities that are associated with current immune-system conditioning.
POTENTIAL APPLICATIONS:
• Increased grafting potential of ACT therapy
• Reduction of systemic toxicities associated with pre-conditioning
• Research Tools for Mammalian Cell Studies
ADVANTAGES:
• Better alternative to the use of Toxic Chemicals
• Reduces side-effects from immune-suppressive chemotherapeutics
DEVELOPMENT-TO-DATE:
The conditioning reagent has been tested for efficacy differences in CAR T-cell therapies in murine and NHP models; showing the ability to reduce systemic toxicity while increasing the response to therapy.