bims-tuinly 2024-12-29 papers

Front Immunol. 2024 ;15 1483254

Clinical-scale, modular manufacturing of tumor-reactive TILs using a closed and automated culture system.

Christina Völzke, Lisa Ehrhardt, Laura Fischer, Peter Maul, Carina Wenzel, Arina Riabinska, Elvira Criado-Moronati, Mike Dienstbier, Jessica Hassel, Danmei Zhang, John B Haanen, Rupert Handgretinger, Ian R Hardy, Bianca Heemskerk, Andrzej Dzionek.

Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, the translation of TIL therapy for patients is still hampered by non-standardized and laborious manufacturing procedures that are expensive and produce highly variable cellular products. To address these limitations, the CliniMACS Prodigy® Tumor Reactive T cell (TRT) Process has been developed. The TRT Process allows the automated isolation, transduction, and expansion of tumor-reactive T cells in a clinically compliant and closed system under GMP conditions. The TRT Process can generate tumor-reactive T cells using several methodologies which reflect clinically relevant applications. It can manage an automated Rapid Expansion Protocol (REP) using GMP-compliant reagents to generate a TIL cell product from solid tumors, including melanoma. Additionally, the TRT Process automates the closed selection of CD137-expressing TILs directly from tumor digest followed by the direct expansion of selected cells. Enriched CD137+ TILs could be robustly expanded even when as few as 1x104 TILs were used to seed the REP phase. These data provide proof-of-concept for the isolation and expansion of tumor-reactive T cells from tumor digest in a closed, automated manner in the CliniMACS Prodigy, allowing for an efficient, simple, and reproducible manufacturing of TIL products. The direct selection of CD137+ TILs from tumor digest removes the need for the pre-REP phase, selects for therapeutically relevant cells, and can dramatically shorten the manufacturing time compared to conventional methods.

Keywords: CD137; CliniMACS Prodigy; GMP compliant cell manufacturing; REP; TILs; automation; tumor reactive T cells

DOI: https://doi.org/10.3389/fimmu.2024.1483254

Front Immunol. 2024 ;15 1497522

Tumor-infiltrating lymphocytes in melanoma: from prognostic assessment to therapeutic applications.

Meshack Bida, Thabiso Victor Miya, Rodney Hull, Zodwa Dlamini.

Malignant melanoma, the most aggressive form of skin cancer, is characterized by unpredictable growth patterns, and its mortality rate has remained alarmingly high over recent decades, despite various treatment approaches. One promising strategy for improving outcomes in melanoma patients lies in the early use of biomarkers to predict prognosis. Biomarkers offer a way to gauge patient outlook early in the disease course, facilitating timely, targeted intervention. In recent years, considerable attention has been given to the immune response's role in melanoma, given the tumor's high immunogenicity and potential responsiveness to immunologic treatments. Researchers are focusing on identifying predictive biomarkers by examining both cancer cell biology and immune interactions within the tumor microenvironment (TME). This approach has shed light on tumor-infiltrating lymphocytes (TILs), a type of immune cell found within the tumor. TILs have emerged as a promising area of study for their potential to serve as both a prognostic indicator and therapeutic target in melanoma. The presence of TILs in melanoma tissue can often signal a positive immune response to the cancer, with numerous studies suggesting that TILs may improve patient prognosis. This review delves into the prognostic value of TILs in melanoma, assessing how these immune cells influence patient outcomes. It explores the mechanisms through which TILs interact with melanoma cells and the potential clinical applications of leveraging TILs in treatment strategies. While TILs present a hopeful avenue for prognostication and treatment, there are still challenges. These include understanding the full extent of TIL dynamics within the TME and overcoming limitations in TIL-based therapies. Advancements in TIL characterization methods are also critical to refining TIL-based approaches. By addressing these hurdles, TIL-focused research may pave the way for improved diagnostic and therapeutic options, ultimately offering better outcomes for melanoma patients.

Keywords: CD4+; CD8+; adoptive cell therapy (ACT); immune checkpoint inhibitors (ICIs); immunotherapy; melanoma; prognosis; tumor-infiltrating lymphocytes

DOI: https://doi.org/10.3389/fimmu.2024.1497522

Curr Oncol. 2024 Nov 25. 31(12): 7476-7493

The Potential of PD-1 and PD-L1 as Prognostic and Predictive Biomarkers in Colorectal Adenocarcinoma Based on TILs Grading.

Nur Rahmah Rasyid, Upik Anderiani Miskad, Muhammad Husni Cangara, Syarifuddin Wahid, Djumadi Achmad, Suryani Tawali, Mardiati Mardiati.

AIM: Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate. Tumor-infiltrating lymphocytes (TILs) play a crucial role in the immune response against tumors. Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are key immune checkpoints regulating T cells in the tumor microenvironment. This study aimed to assess the relationships among PD-1 expression on TILs, PD-L1 expression in tumors, and TIL grading in colorectal adenocarcinoma.
METHODS: A cross-sectional design was employed to analyze 130 colorectal adenocarcinoma samples. The expression of PD-1 and PD-L1 was assessed through immunohistochemistry. A semi-quantitative scoring system was applied. Statistical analysis with the chi-square test was performed to explore correlations, with the data analyzed in SPSS version 27.
RESULTS: PD-1 expression on TILs significantly correlated with a higher TIL grading (p < 0.001), while PD-L1 expression in tumors showed an inverse correlation with TIL grading (p < 0.001).
CONCLUSIONS: The expression of PD-1 on TILs and PD-L1 on tumor cells correlated significantly with the grading of TILs in colorectal adenocarcinoma. This finding shows potential as a predictive biomarker for PD-1/PD-L1 blockade therapy. Further studies are needed to strengthen these results.

Keywords: PD-1; PD-L1; biomarkers; colorectal cancer; immunotherapy; tumor infiltrating lymphocytes

DOI: https://doi.org/10.3390/curroncol31120552