Surgical Considerations for Tumor Tissue Procurement to Obtain Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy

Abstract

Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs), an investigational cellular therapy, has demonstrated antitumor efficacy in patients with advanced solid tumors, including melanoma. Tumor-infiltrating lymphocyte cell therapy involves surgical resection of a patient's tumor, ex vivo TIL expansion under conditions that overcome immunosuppressive responses elicited by the tumor and the tumor microenvironment, administration of a lymphodepleting regimen, and infusion of the final TIL cell therapy product back into the patient followed by interleukin 2 administration to support T-cell activity. The surgeon plays a central role in patient identification and tumor selection—steps that are critical for successful outcomes of TIL cell therapy. Commercialization of TIL cell therapy and its broader access to patients will require education and collaboration among surgeons, oncologists, and cellular therapists. This review highlights the unique role that surgeons will play in the implementation of TIL cell therapy and serves as a contemporary report of best practices for patient selection and tumor resection methods.

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study

“…Surgical best practices for tumor resection for TIL manufacturing are well established to address possible practice variations. 60 Further innovation is underway to develop TIL regimens that use IL-2 analogs to enhance antitumor responses by continuous support of growth and activity of the infused TIL product, but also mitigate the toxicities associated with currently available recombinant IL-2. Moreover, efforts to reduce the doses of available cytotoxic agents or develop novel lymphodepletion regimens may allow for broader use.…”

Expert consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy

“…Surgical considerations and best practices for tumor tissue procurement have been previously described by Mullinax et al . 21 …”

Biomarkers for response to TIL therapy: a comprehensive review

“…8 48 Since myelotoxic CT will be required a few weeks after surgery, anatomic sites that allow minimally invasive procedures and minimize complications (eg, subcutaneous/soft tissue nodules, or lymph nodes) are preferable, 13 while those with a higher risk of bacterial contamination (eg, skin, bowel lesions, preirradiated, or ulcerated tumors) should be avoided if possible. 49 Procurement from secondary lymphoid organs (eg, the spleen or bowel) might pose limitations due to bystander non-tumorreactive lymphocytes that could preferentially expand within the culture. 49 Lymph nodes or peripheral tumor areas closer to blood or lymphatic vessels are preferred, in contrast to necrotic, hemorrhagic, or adipose areas, which negatively correlate with TIL growth.…”

“…49 Procurement from secondary lymphoid organs (eg, the spleen or bowel) might pose limitations due to bystander non-tumorreactive lymphocytes that could preferentially expand within the culture. 49 Lymph nodes or peripheral tumor areas closer to blood or lymphatic vessels are preferred, in contrast to necrotic, hemorrhagic, or adipose areas, which negatively correlate with TIL growth. 50 Regarding TIL expansion, a short ex vivo cell culture time is a robust biomarker for response to TIL-ACT.…”