Innovative CAR-TIL immunotherapy against melanoma
Overview
Tab Title Description
Study type
ObservationalDescribes the nature of a clinical study. Types include:
- Observational study — observes people and measures outcomes without affecting results.
- Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
- Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
Study IDs
Site IRB
- Jacksonville, Florida: 22-013458
Sponsor Protocol Number: MC9324
About this study
The chimeric antigen receptor (CAR) T-cell therapy is a revolutionary cellular immunotherapy strategy that has transformed the treatment of B cell malignancies by engineering T cells to recognize B cell specific tumor markers; however, attempts to treat solid tumors with CAR T-cells have identified unique challenges that have rendered CAR T cells less effective against these tumors. Conventional CARs are designed to target tumor-associated antigens, but antigenic heterogeneity and the variable nature of surface antigen expression provide escape mechanisms for solid tumors from CAR T-cell attack. [1, 2] The solid tumor stroma acts as an immunosuppressive cloud that impedes the homing of peripheral CAR T-cells into the tumor microenvironment (TME). The hostile TME can also drive CAR T-cells to functional exhaustion and metabolic dysfunction, thus blunting the therapeutic efficacy of CAR T-cells.[3] Oncolytic viruses or radiation that generate local inflammation in the TME have been shown to promote T cell homing and infiltration [4] but do not address the exhaustion of tumor infiltrating lymphocytes (TILs). The PD-1/PD-L1 cascade allows tumors to evade the immune system by suppressing T cell function within the TME. [5, 6] An ideal adoptive cellular therapy must possess the ability to not only return to the site of the tumor but must also retain cytotoxic potential after a recognition event. We present here a CAR design that allows PD-1 to recognize PD-L1 on the tumor; however, the intracellular CAR design is one that results in T cell activation as opposed to inhibition. We hypothesize that targeting melanoma with a PD-1 (MC9324) CAR TIL therapy would capitalize on the tumor homing machinery of the TIL to drive the CAR TIL to the tumor where engagement of the PD-1 domain of the CAR with PD-L1 on the tumor cell would result in T cell cytotoxic killing.
Participation eligibility
Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Subject population (children, adults, groups): All eligible patients will be encouraged to enroll regardless of ethnicity, gender, or race. Ideal tissue collection will be from surgically removed tissue. Patient populations to consider include:
- Stage III proceeding directly to resection
- Stage III post neoadjuvant therapy proceeding to resection
- Limited stage IV undergoing metastasectomy
Inclusion Criteria:
- are 16 years of age or older
- have histologic evidence of melanoma
- have an understanding of the protocol and its requirements, risks, and discomforts
- are willing to provide excess surgical tissue that is not needed for clinical purposes
- are willing to provide peripheral blood samples at the time points mentioned in the protocol
- are able and willing to sign an informed consent.
Exclusion Criteria:
- inability on the part of the patient to understand the informed consent or be compliant with the protocol
- history of a serious or life-threatening allergic reaction to local anesthetics (i.e., lidocaine, xylocaine)
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 9/4/2024. Questions regarding updates should be directed to the study team contact.
Participating Mayo Clinic locations
Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.
| Mayo Clinic Location |
Status |
Contact |
Jacksonville, Fla.
Mayo Clinic principal investigator Roxana Dronca, M.D. |
Open for enrollment |
Contact information:
Cancer Center Clinical Trials Referral Office
(855) 776-0015
|
More information
Publications
Publications are currently not available