Tumor-infiltrating lymphocytes

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Tumor infiltrating lymphocytes (TILs) are a type of white blood cell found in tumors. TILs are implicated in killing tumor cells, and the presence of lymphocytes in tumors is often associated with better clinical outcomes.[1][2]

Adoptive cell transfer therapy[edit]

The use of TILs as an adoptive cell transfer therapy to treat cancer has been pioneered by Dr. Steven Rosenberg at the National Cancer Institute. Autologous lymphocytes are isolated from patients’ tumors and grown to very large numbers of cells in vitro. Prior to TIL treatment, patients are given nonmyeloablative chemotherapy to deplete native lymphocytes that can suppress tumor killing. Once lymphodepletion is completed, patients are then infused with TILs in combination with interleukin 2 (IL-2). Lion Biotechnologies is currently developing adoptive cell transfer with TILs for the treatment of cancer.

Melanoma[edit]

Several clinical trials have been conducted using TILs to treat patients with metastatic melanoma, a deadly form of skin cancer. Tumor reduction of 50% or more was observed in about half of melanoma patients treated with TILs.[3][4][5][6] Some patients experienced complete responses with no detectable tumor remaining years after TIL treatment.[7]

Other cancers[edit]

Clinical trials using TILs to treat digestive tract cancers, such as colorectal cancer,[8] and cancers associated with the human papilloma virus (HPV), such as cervical cancer,[9] are ongoing. Scientists are also investigating whether TILs can be used to treat other tumors, including lung, ovarian, bladder, and breast.

References[edit]

  1. ^ Vánky F, Klein E, Willems J et al. (1986). "Lysis of autologous tumor cells by blood lymphocytes tested at the time of surgery. Correlation with the postsurgical clinical course". Cancer Immunology, Immunotherapy 21 (1): 69–76. doi:10.1007/BF00199380. PMID 3455878. 
  2. ^ Zhang L, Conejo-Garcia JR, Katsaros D et al. (January 2003). "Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer". The New England Journal of Medicine 348 (3): 203–13. doi:10.1056/NEJMoa020177. PMID 12529460. 
  3. ^ Dudley ME, Yang JC, Sherry R et al. (November 2008). "Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens". Journal of Clinical Oncology 26 (32): 5233–9. doi:10.1200/JCO.2008.16.5449. PMC 2652090. PMID 18809613. 
  4. ^ Radvanyi LG, Bernatchez C, Zhang M et al. (December 2012). "Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients". Clinical Cancer Research 18 (24): 6758–70. doi:10.1158/1078-0432.CCR-12-1177. PMC 3525747. PMID 23032743. 
  5. ^ Pilon-Thomas S, Kuhn L, Ellwanger S et al. (October 2012). "Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma". Journal of Immunotherapy 35 (8): 615–20. doi:10.1097/CJI.0b013e31826e8f5f. PMID 22996367. 
  6. ^ Besser MJ, Shapira-Frommer R, Treves AJ et al. (May 2010). "Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients". Clinical Cancer Research 16 (9): 2646–55. doi:10.1158/1078-0432.CCR-10-0041. PMID 20406835. 
  7. ^ Rosenberg SA, Yang JC, Sherry RM et al. (July 2011). "Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy". Clinical Cancer Research 17 (13): 4550–7. doi:10.1158/1078-0432.CCR-11-0116. PMC 3131487. PMID 21498393. 
  8. ^ Clinical trial number NCT01174121 for "A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers" at ClinicalTrials.gov
  9. ^ Clinical trial number NCT01585428 for "A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human Papillomavirus-Associated Cancers" at ClinicalTrials.gov

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