title: Phase I study to evaluate toxicity and feasibility of intratumoral injection of α-gal glycolipids in patients with advanced melanoma.
abstract: Effective uptake of tumor cell-derived antigens by antigen-presenting cells is achieved pre-clinically by in situ labeling of tumor with α-gal glycolipids that bind the naturally occurring anti-Gal antibody. We evaluated toxicity and feasibility of intratumoral injections of α-gal glycolipids as an autologous tumor antigen-targeted immunotherapy in melanoma patients (pts). Pts with unresectable metastatic melanoma, at least one cutaneous, subcutaneous, or palpable lymph node metastasis, and serum anti-Gal titer ≥1:50 were eligible for two intratumoral α-gal glycolipid injections given 4 weeks apart (cohort I: 0.1 mg/injection; cohort II: 1.0 mg/injection; cohort III: 10 mg/injection). Monitoring included blood for clinical, autoimmune, and immunological analyses and core tumor biopsies. Treatment outcome was determined 8 weeks after the first α-gal glycolipid injection. Nine pts received two intratumoral injections of α-gal glycolipids (3 pts/cohort). Injection-site toxicity was mild, and no systemic toxicity or autoimmunity could be attributed to the therapy. Two pts had stable disease by RECIST lasting 8 and 7 months. Tumor nodule biopsies revealed minimal to no change in inflammatory infiltrate between pre- and post-treatment biopsies except for 1 pt (cohort III) with a post-treatment inflammatory infiltrate. Two and four weeks post-injection, treated nodules in 5 of 9 pts exhibited tumor cell necrosis without neutrophilic or lymphocytic inflammatory response. Non-treated tumor nodules in 2 of 4 evaluable pts also showed necrosis. Repeated intratumoral injections of α-gal glycolipids are well tolerated, and tumor necrosis was seen in some tumor nodule biopsies after tumor injection with α-gal glycolipids.
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA. mralbert@wisc.edu.|Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. mralbert@wisc.edu.|Medical Service, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. mralbert@wisc.edu.|University of Wisconsin Clinical Sciences Center, Room K6/530, 600 Highland Avenue, Madison, WI, 53792, USA. mralbert@wisc.edu.
authors.forename: Mark R
authors.identifier: 0000-0002-6499-517X
authors.initials: MR
authors.lastname: Albertini
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.|Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Ranheim
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.|Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Zuleger
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.|Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sondel
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.|Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Hank
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Medical Service, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Bridges
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.|Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Newton
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.|Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: McFarland
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Collins
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Clements
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Henry
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.|Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Neuman
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI, USA.|Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Weber
authors.affiliation: Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Giles
authors.initials: G
authors.lastname: Whalen
authors.affiliation: Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Uri
authors.initials: U
authors.lastname: Galili
mesh_terms: D000328:Adult; D000368:Aged; D005240:Feasibility Studies; D005260:Female; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D015552:Injections, Intralesional / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged
chemical_list: D006017:Glycolipids
keywords: Cancer vaccines; Immunotherapy; Melanoma; α-Gal glycolipids