Ocular and Systemic Autoimmunity after Successful Tumor-Infiltrating Lymphocyte Immunotherapy for Recurrent, Metastatic Melanoma

Yeh, Steven; Karne, Neel K.; Kerkar, Sid P.; Heller, Charles K.; Palmer, Douglas C.; Johnson, Laura A.; Li, Zhuqing; Bishop, Rachel; Wong, Wai T.; Sherry, Richard M.; Yang, James Chih‐Hsin; Dudley, Mark E.; Restifo, Nicholas P.; Rosenberg, Steven A.; Nussenblatt, Robert B.

doi:10.1016/j.ophtha.2008.12.004

Cited by 90 publications

(70 citation statements)

References 30 publications

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“…This structure of the eye was clearly thickened compared with the mice receiving pmel T cells alone. These findings are similar to recently published data on uveitis in a mouse model and a cutaneous melanoma patient who was treated with immunotherapy (22,23). Importantly, treatment with ACT and peptide vaccination caused a significant delay in B16 melanoma outgrowth in the eye compared with naïve mice (Fig.…”

Section: In Vivo Effector Functions Of Transferred T Cellssupporting

confidence: 91%

“…Enriched spleen cells (3 × 10 6 CD8 + T lymphocytes) were adoptively transferred by injection into the tail vein. Mice were immunized 1 day later by shaving the left flank and s.c. injecting 150 μg of homologous human gp100 20-39 KVP (AVGALKVPRNQDWLGVPRQL) or mouse gp100 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] EGS (AVGALEGSRNQDWLGVPRQL) peptide solved in PBS. Toll-like receptor (TLR) ligands were simultaneously applied: 60 mg of Aldara cream containing 5% imiquimod on the skin at the injection site or 25 μg of CpG 1826 from the Leiden Institute of Chemistry.…”

Section: Adoptive Cell Transfer and Immunization Of Micementioning

confidence: 99%

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Peptide Vaccination after T-Cell Transfer Causes Massive Clonal Expansion, Tumor Eradication, and Manageable Cytokine Storm

Sluijter

Versluis

et al. 2010

Cancer Research

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Adoptive T-cell transfer (ACT) is successfully applied as a cancer treatment that is based on the activation and effector functions of tumor-specific T cells. Here, we present results from a mouse model in which ACT is combined with a long peptide-based vaccine comprising gp100 T-cell epitopes. Transferred CD8 + T cells expanded up to 1,000-fold after peptide vaccination, leading to a 3-fold increase in white blood cell count and a very high frequency in the generation of antigen-specific memory T cells, the generation of which tended to correlate with effective antitumor responses. An enormous pool of effector T cells spread widely to different tissues, including the skin and the immune-privileged eye, where they mediate tumor eradication. Importantly, these striking T-cell dynamics occurred in immunocompetent mice without prior hematologic conditioning. Continued activation of the specific T-cell pool by vaccination led to strong T-cell-mediated cytokine storm and lethality due to multiorgan failure. However, this immunopathology could be prevented by controlling the rapid biodistribution of the peptide or by using a weakly agonistic peptide. Together, these results identify a peptide vaccination strategy that can potently accentuate effective ACT in non-lymphodepleted hosts.

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Section: In Vivo Effector Functions Of Transferred T Cellssupporting

confidence: 91%

Section: Adoptive Cell Transfer and Immunization Of Micementioning

confidence: 99%

Peptide Vaccination after T-Cell Transfer Causes Massive Clonal Expansion, Tumor Eradication, and Manageable Cytokine Storm

Sluijter

Versluis

et al. 2010

Cancer Research

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“…Tumor regression without induction of autoimmunity has been reported (9, 58, 59) using T cells with relatively low reactivity against tumor antigens; high-avidity T cells are often associated with autoimmunity (6,27,45,59). Our results showed that antitumor activity and autoimmunity are coupled and have a similar kinetic threshold; reducing autoimmunity cannot be accomplished without sacrificing efficacy of tumor killing.…”

Section: Discussionmentioning

confidence: 99%

“…Autoimmune destruction of melanocytes in the eye (ocular autoimmunity) has been observed both in human (6,27) and mouse (26) melanoma ACT. To determine whether autoimmunity correlates with TCR antitumor activities, we selected five TCRs showing various antitumor activities (high, L2G2 and R6C12; intermediate, K4H5 and 5CE2; and low, W2C8; Fig.…”

Section: Was Correlated With Tcr Avidity (C) or Affinity (D) (E And F)mentioning

confidence: 99%

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T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy

Shi

Malecek

Johnson

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

203

215

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T cells expressing antigen-specific T-cell receptors (TCRs) can mediate effective tumor regression, but they often also are accompanied by autoimmune responses. To determine the TCR affinity threshold defining the optimal balance between effective antitumor activity and autoimmunity in vivo , we used a unique self-antigen system comprising seven human melanoma gp100(209–217)-specific TCRs spanning physiological affinities (1–100 μM). We found that in vitro and in vivo T-cell responses are determined by TCR affinity, except in one case that was compensated by substantial CD8 involvement. Strikingly, we found that T-cell antitumor activity and autoimmunity are closely coupled but plateau at a defined TCR affinity of 10 µM, likely due to diminished contribution of TCR affinity to avidity above the threshold. Together, these results suggest that a relatively low-affinity threshold is necessary for the immune system to avoid self-damage, given the close relationship between antitumor activity and autoimmunity. The low threshold, in turn, indicates that adoptive T-cell therapy treatment strategies using in vitro-generated high-affinity TCRs do not necessarily improve efficacy.

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TIL Therapy in Lung Cancer: Current Progress and Perspectives

Hu,

Bian,

2024

Advanced Science

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Lung cancer remains the most prevalent malignant tumor worldwide and is the leading cause of cancer‐related mortality. Although immune checkpoint blockade has revolutionized the treatment of advanced lung cancer, many patients still do not respond well, often due to the lack of functional T cell infiltration. Adoptive cell therapy (ACT) using expanded immune cells has emerged as an important therapeutic modality. Tumor‐infiltrating lymphocytes (TIL) therapy is one form of ACT involving the administration of expanded and activated autologous T cells derived from surgically resected cancer tissues and reinfusion into patients and holds great therapeutic potential for lung cancer. In this review, TIL therapy is introduced and its suitability for lung cancer is discussed. Then its historical and clinical developments are summarized, and the methods developed up‐to‐date to identify tumor‐recognizing TILs and optimize TIL composition. Some perspectives toward future TIL therapy for lung cancer are also provided.

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Ocular and Systemic Autoimmunity after Successful Tumor-Infiltrating Lymphocyte Immunotherapy for Recurrent, Metastatic Melanoma

Cited by 90 publications

References 30 publications

Peptide Vaccination after T-Cell Transfer Causes Massive Clonal Expansion, Tumor Eradication, and Manageable Cytokine Storm

Peptide Vaccination after T-Cell Transfer Causes Massive Clonal Expansion, Tumor Eradication, and Manageable Cytokine Storm

T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy

TIL Therapy in Lung Cancer: Current Progress and Perspectives

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