Literature DB >> 22993330

Cancer immunotherapy by intratumoral injection of α-gal glycolipids.

Giles F Whalen1, Mary Sullivan, Bilal Piperdi, Wahid Wasseff, Uri Galili.   

Abstract

UNLABELLED: AIM/
BACKGROUND: To determine the feasibility and safety of intratumoral α-gal glycolipids injection for conversion of human tumors into autologous Tumor Associated Antigens (TAA) vaccine. α-Gal glycolipids bind anti-Gal--the most abundant antibody in humans. Pre-clinical studies indicated that injected α-gal glycolipids insert into tumor cell membranes, bind anti-Gal and target tumor cells to Antigen Presenting Cells, thereby converting tumors into autologous TAA vaccines. We hypothesized that α-gal glycolipids might have similar utility in humans. PATIENTS AND METHODS: Eleven patients with advanced solid tumors received one intratumoral injection of 0.1 mg, 1 mg, or 10 mg α-gal glycolipids. The primary endpoint was dose-limiting toxicity (DLT) within 4 weeks. Secondary endpoints included long-term toxicity, autoimmunity, radiological tumor response and survival.
RESULTS: There were no DLT and no clinical or laboratory evidence of autoimmunity, or any other toxicity. Few patients had an unexpectedly long survival.
CONCLUSION: Intratumoral injection of α-gal glycolipids is feasible and safe for inducing a protective anti-tumor immune response.

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Year:  2012        PMID: 22993330

Source DB:  PubMed          Journal:  Anticancer Res        ISSN: 0250-7005            Impact factor:   2.480


  9 in total

1.  Reply to Mackenzie: A comparison of Neu5Gc and α-gal xenoantigens.

Authors:  Oliver M T Pearce; Annie N Samraj; Heinz Läubli; Nissi M Varki; Ajit Varki
Journal:  Proc Natl Acad Sci U S A       Date:  2015-02-20       Impact factor: 11.205

Review 2.  Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer.

Authors:  Trisha A Rettig; Julie N Harbin; Adelaide Harrington; Leonie Dohmen; Sherry D Fleming
Journal:  Clin Immunol       Date:  2015-07-02       Impact factor: 3.969

3.  Phase I study to evaluate toxicity and feasibility of intratumoral injection of α-gal glycolipids in patients with advanced melanoma.

Authors:  Mark R Albertini; Erik A Ranheim; Cindy L Zuleger; Paul M Sondel; Jacquelyn A Hank; Alan Bridges; Michael A Newton; Thomas McFarland; Jennifer Collins; Erin Clements; Mary Beth Henry; Heather B Neuman; Sharon Weber; Giles Whalen; Uri Galili
Journal:  Cancer Immunol Immunother       Date:  2016-05-20       Impact factor: 6.968

Review 4.  Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits.

Authors:  Uri Galili
Journal:  Immunology       Date:  2013-09       Impact factor: 7.397

Review 5.  Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes.

Authors:  Uri Galili
Journal:  Vaccine       Date:  2020-08-19       Impact factor: 3.641

6.  In situ conversion of tumors into autologous tumor-associated antigen vaccines by intratumoral injection of α-gal glycolipids.

Authors:  Uri Galili
Journal:  Oncoimmunology       Date:  2013-01-01       Impact factor: 8.110

7.  Epithelial ovarian cancer stem-like cells expressing α-gal epitopes increase the immunogenicity of tumor associated antigens.

Authors:  Xiaofen Yao; Zhangli Dong; Qiuwan Zhang; Qian Wang; Dongmei Lai
Journal:  BMC Cancer       Date:  2015-12-16       Impact factor: 4.430

Review 8.  Characteristics of α-Gal epitope, anti-Gal antibody, α1,3 galactosyltransferase and its clinical exploitation (Review).

Authors:  Guoli Huai; Ping Qi; Hongji Yang; Yi Wang
Journal:  Int J Mol Med       Date:  2015-10-30       Impact factor: 4.101

9.  AGI-134: a fully synthetic α-Gal glycolipid that converts tumors into in situ autologous vaccines, induces anti-tumor immunity and is synergistic with an anti-PD-1 antibody in mouse melanoma models.

Authors:  Stephen M Shaw; Jenny Middleton; Kim Wigglesworth; Amber Charlemagne; Oliver Schulz; Melanie S Glossop; Giles F Whalen; Robert Old; Mike Westby; Chris Pickford; Rinat Tabakman; Irit Carmi-Levy; Abi Vainstein; Ella Sorani; Arik A Zur; Sascha A Kristian
Journal:  Cancer Cell Int       Date:  2019-12-19       Impact factor: 5.722

  9 in total

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