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Cell Therapy With TILs: Training and Taming T Cells to Fight Cancer.

ABSTRACT: The rationale behind cancer immunotherapy is based on the unequivocal demonstration that the immune system plays an important role in limiting cancer initiation and progression. Adoptive cell therapy (ACT) is a form of cancer immunotherapy that utilizes a patient's own immune cells to find and eliminate tumor cells, however, donor immune cells can also be employed in some cases. Here, we focus on T lymphocyte (T cell)-based cancer immunotherapies that have gained significant attention after initial discoveries that graft-versus-tumor responses were mediated by T cells. Accumulating knowledge of T cell development and function coupled with advancements in genetics and data science has enabled the use of a patient's own (autologous) T cells for ACT (TIL ACTs). In TIL ACT, tumor-infiltrating lymphocytes (TILs) are collected from resected tumor material, enhanced and expanded ex-vivo, and delivered back to the patient as therapeutic agents. ACT with TILs has been shown to cause objective tumor regression in several types of cancers including melanoma, cervical squamous cell carcinoma, and cholangiocarcinoma. In this review, we provide a brief history of TIL ACT and discuss the current state of TIL ACT clinical development in solid tumors. We also discuss the niche of TIL ACT in the current cancer therapy landscape and potential strategies for patient selection.

SUBMITTER: Kumar A

PROVIDER: S-EPMC8204054 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeDigital 3D exoscopes have been recently introduced as an alternative to a surgical microscope in microneurosurgery. We designed a laboratory training program to facilitate and measure the transition from microscope to exoscope. Our aim was to observe the effect of a one-year active training on microsurgical skills with the exoscope by repeating a standardized test task at several time points during the training program.MethodsTwo board-certified neurosurgeons with no previous exoscope experience performed the same test tasks in February, July, and November during a 12-month period. In between the test tasks, both participants worked with the exoscope in the laboratory and assisted during clinical surgeries on daily basis. Each of the test segments consisted of repeating the same task 10 times during one week. Altogether, 60 test tasks were performed, 30 each. The test task consisted of dissecting and harvesting the ulnar and radial arteries of the second segment of a chicken wing using an exoscope (Aesculap AEOS). Each dissection was recorded on video and analyzed by two independent evaluators. We measured the time required to complete the task as well as several metrics for evaluating the manual skills of the dissection and handling of the exoscope system.ResultThere was a clear reduction in dissection time between the first and the last session, mean 34 min (SD 5.96) vs. 26 min (SD 8.69), respectively. At the end of the training, both neurosurgeons used the exoscope more efficiently utilizing more available options of the device. There was correlation between the dissection time and several of the factors we used for evaluating the work flow: staying in focus, zoom control, reduction of unnecessary movements or repetitive manual motions, manipulation technique of the vessel under dissection, handling of the instruments, and using them for multiple dissection purposes (stretching, cutting, and splitting).ConclusionContinuous, dedicated long-term training program is effective for microsurgical skill development when switching from a microscope to an exoscope. With practice, the micromotor movements become more efficient and the use of microinstruments more versatile.

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Cell Therapy With TILs: Training and Taming T Cells to Fight Cancer.

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