The safety and efficacy of TIL cell therapies are under investigation and have not been established. There are no guarantees that TIL cell therapies will receive US FDA approval for the uses being investigated.

Discover the potential of TIL therapy

Understanding TIL:
Part of the body’s natural response to cancer

  • The cells of the immune system perform immunosurveillance while circulating throughout the body1
  • As part of the normal immune response, TIL migrate to the tumor site through recognition of chemokines produced by the tumor. TIL recognize tumors through tumor-specific antigens (TSAs) and can cause lysis to tumor cells2-5
  • Solid tumors are extremely heterogeneous. Studies suggest that TIL from each individual are unique and polyclonal, which means that TIL may be able to recognize an array of known tumor antigens and unique patient-specific antigens4,6,7
body's natural response to cancer

Watch how TIL recognize and lyse tumor cells

TIL are important for helping to eradicate tumor cells1,8

TIL recognize and eradicate tumor cells in 3 steps:

TIL can recognize the TSAs on the surface of tumor cells9
The TIL can become activated and release perforin, a pore-forming protein9
The newly formed pores allow for the delivery of granzymes, which cause lysis of the target cancer cell9

Multiple studies have shown that the presence and activity of endogenous TIL is associated with better survival as an independent prognostic factor in various types of cancers, including10-14:

  • Advanced melanoma
  • Cervical cancer
  • Non-small cell lung cancer

Cancer prevails when the tumor microenvironment overpowers the immune response15

Solid tumors are highly heterogeneous diseases (both intra- and inter-tumorally) that present unique considerations16

TIL is unique and polyclonal
  • Many oncogenic driver mutations, regulating a multitude of critical cellular pathways, are implicated in solid tumor development and progression17
  • With such diversity of disease, there is strong evidence to support the investigation of therapies that may be able to recognize multiple antigens and mount an offense against the tumor18
TIL is unique and polyclonal

Many patients with solid tumors have benefitted from immune checkpoint inhibitors (ICIs). However, there remains significant unmet need for patients who have not responded to or who have progressed on ICIs. When patients are refractory or relapse on immunotherapy or chemotherapy, subsequent treatments provide limited responses.19,20

Researching TIL: Investigating TIL therapy to help fight cancer

  • TIL are being investigated as a cellular immunotherapy, as clinical studies have shown that they can recognize and eradicate tumor cells21-23
  • TIL cellular therapy is the concept of extracting, isolating, and expanding a patient's TIL and reinfusing billions of these TIL back into the patient21
Cellular immunotherapy

IOVANCE Biotherapeutics is committed to deepening the understanding of TIL and optimizing TIL technology to help shape the next chapter of TIL cell therapy. Considerations of TIL cell therapy:

Trained staff for an automated process

Scalability: A high level of investment is required. Specialized facilities and trained production staff are needed in order to automate the expansion process.23

expanding patient TIL therapy

T cell invigoration: A successful process can rejuvenate T cells so that they can recognize and eradicate tumor cells.24

Cell amplification

Time: Improved turnaround time for cell amplification can enable faster delivery to patients as well as select for "younger" and more active TIL.23

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Contact Us

Iovance Biotherapeutics

999 Skyway Road

Suite 150

San Carlos, CA 94070

Phone: 650-260-7120

References: 1. Badalamenti G, Fanale D, Incorvaia L, et al. Role of tumor-infiltrating lymphocytes in patients with solid tumors: can a drop dig a stone? Cell Immun. 2019;343(103753):1-8. 2. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2018;12(4):269-281. 3. Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986;233:1318-1321. 4. Antohe M, Nedelcu RI, Nichita L, et al. Tumor infiltrating lymphocytes: the regulator of melanoma evolution (review). Oncol Lett. 2019;17:4155-4161. 5. Bethune MT and Joglekar AV. Personalized T cell-mediated cancer immunotherapy: progress and challenges. Curr Opin Biotechnol. 2017;48:142-152. 6. Yossef R, Tran E, Deniger DC, et al. Enhanced detection of neoantigen-reactive T cells targeting unique and shared oncogenes for personalized cancer immunotherapy. JCI Insight. 2018;3(19):e122467. 7. Geukes Foppen MH, Donia M, Svane IM, Haanen JBAG. Tumor-infiltrating lymphocytes for the treatment of metastatic cancer. Mol Oncol. 2015;9:1918-1935. 8. Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology. 2007;121:1-14. 9. Chávez-Galán L, Arenas-Del Angel MC, Zenteno E, Chávez R, Lascurain R. Cell death mechanisms induced by cytotoxic lymphocytes. Cell Mol Immunol. 2009;6(1):15-25. 10. Fu Q, Chen N, Ge C, et al. Prognostic value of tumor-infiltrating lymphocytes in melanoma: a systematic review and meta-analysis. Oncoimmunology. 2019;8(7):1-14. 11. Stevanović S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus–targeted tumor-infiltrating T cells. J Clin Oncol. 2015;33(14):1543-1550. 12. Stevanović S, Helman SR, Wunderlich JR, et al. A phase II study of tumor-infiltrating lymphocyte therapy for human papillomavirus-associated epithelial cancers. Clin Cancer Res. 2019;25(5):1486-1493. 13. Schalper KA, Brown J, Carvajal-Hausdorf D, et al. Objective measurement and clinical significance of TILs in non-small cell lung cancer. J Natl Cancer Inst. 2015;107(3):1-9. 14. Clemente CG, Mihm MC, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer. 1996;77(7):1303-1310. 15. Ochsenbein AF, Klenerman P, Karrer U, et al. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci. 1999;96:2233-2238. 16. Lawrence MS, Stojanov P, Polak P, et al. Mutational heterogeneity in cancer and the search for new cancer genes. Nature. 2013;499(7457):214-218. 17. Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harb Perspect Med. 2015;5:1-21. 18. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015;348(6230):62-68. 19. Darvin P, Toor SM, Nair VS, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018;50(12):165. 20. Nowicki TS, Hu-Lieskovan S, Ribas A. Mechanisms of resistance to PD-1 and PD-L1 blockade. Cancer J. 2018;24(1):47-53. 21. Rosenberg SA, Yannelli JR, Yang JC, et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst. 1994;86(15):1159-1166. 22. Topalian SL, Solomon D, Avis FP, et al. Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol. 1988;6(5):839-853. 23. Rohaan MW, Van den Berg JH, Kvistborg P, Haanen JBAG. Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option. J Immunother Cancer. 2018;6(102):1-16. doi: 10.1186/s40425-018-0391-1 24. Wherry EJ. T cell exhaustion. Nature. 2011;12(6):492-499.