Augmentation of interleukin-2-induced activation of human melanoma tumor-infiltrating lymphocytes by heteroconjugate antibody

1991 ◽  
Vol 33 (4) ◽  
pp. 247-254 ◽  
Author(s):  
Paul F. Mansfield ◽  
Michael G. Rosenblum ◽  
James L. Murray ◽  
Kyogo Itoh
Keyword(s):  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Human Melanoma ◽  
Melanoma Tumor ◽  
Infiltrating Lymphocytes

scholarly journals Expansion and Characterization of Human Melanoma Tumor-Infiltrating Lymphocytes (TILs)

PLoS ONE ◽  
2010 ◽  
Vol 5 (11) ◽  
pp. e13940 ◽  
Author(s):  
Linh T. Nguyen ◽  
Pei Hua Yen ◽  
Jessica Nie ◽  
Nicole Liadis ◽  
Danny Ghazarian ◽  
...  
Keyword(s):  
Tumor Infiltrating Lymphocytes ◽  
Human Melanoma ◽  
Melanoma Tumor ◽  
Infiltrating Lymphocytes

Lymphokine production by human melanoma tumor-infiltrating lymphocytes

1992 ◽  
Vol 35 (3) ◽  
pp. 211-217 ◽  
Author(s):  
Marie A. Salmeron ◽  
Tatsuo Morita ◽  
Hidetoshi Seki ◽  
Chris D. Platsoucas ◽  
Kyogo Itoh
Keyword(s):  
Tumor Infiltrating Lymphocytes ◽  
Human Melanoma ◽  
Melanoma Tumor ◽  
Lymphokine Production ◽  
Infiltrating Lymphocytes

scholarly journals A cytokine receptor-masked IL2 prodrug selectively activates tumor-infiltrating lymphocytes for potent antitumor therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eric J. Hsu ◽  
Xuezhi Cao ◽  
Benjamin Moon ◽  
Joonbeom Bae ◽  
Zhichen Sun ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoint Blockade ◽  
Targeting Therapy ◽  
Protease Substrate ◽  
Reduced Toxicity ◽  
Infiltrating Lymphocytes ◽  
Receptor Beta

AbstractAs a potent lymphocyte activator, interleukin-2 (IL-2) is an FDA-approved treatment for multiple metastatic cancers. However, its clinical use is limited by short half-life, low potency, and severe in vivo toxicity. Current IL-2 engineering strategies exhibit evidence of peripheral cytotoxicity. Here, we address these issues by engineering an IL-2 prodrug (ProIL2). We mask the activity of a CD8 T cell-preferential IL-2 mutein/Fc fusion protein with IL2 receptor beta linked to a tumor-associated protease substrate. ProIL2 restores activity after cleavage by tumor-associated enzymes, and preferentially activates inside tumors, where it expands antigen-specific CD8 T cells. This significantly reduces IL-2 toxicity and mortality without compromising antitumor efficacy. ProIL2 also overcomes resistance of cancers to immune checkpoint blockade. Lastly, neoadjuvant ProIL2 treatment can eliminate metastatic cancer through an abscopal effect. Taken together, our approach presents an effective tumor targeting therapy with reduced toxicity.

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