Researchers are testing the possible applicability of α-gal glycolipids—antigens present in rabbits—as a novel immunotherapy in humans with melanoma, with some success, according to results published online in the Journal of Cancer Immunology, Immunotherapy. In a small study, researchers from the University of Washington-Madison, Madison, WI, found that repeated α-gal glycolipid injections into tumors in patients with metastatic melanoma were well tolerated and brought about tumor necrosis in some.
Although α-gal glycolipid—an antigen present in the blood and tissues of rabbits and other non-primate mammals—is not present in humans and some monkeys, sufficient quantities of natural anti-α-gal antibodies do exist in humans, and confer the ability to detect the α-gal glycolipids as intruders. Conceivably, injecting α-gal glycolipids into tumors may alert T cells—and consequently the immune system—to locate and kill the cancer cells.
“This treatment has the theoretical potential to convert treated tumors into ‘personalized’ vaccines, effectively instructing the immune system to recognize tumor cells as cells that ought to be destroyed,” said lead author Mark Albertini, MD, associate professor of medicine hematology/oncology and melanoma specialist, University of Wisconsin Carbone Cancer Center, Madison, WI.
Thus, Dr. Albertini and fellow researchers conducted this small, dose-escalation study based on earlier pre-clinical studies to assess the clinical safety of repeated α-gal glycolipids injections into tumors of patients with metastatic melanoma.
They enrolled nine advanced melanoma patients with unresectable metastatic melanoma, at least one cutaneous, subcutaneous or palpable lymph node metastasis, and serum anti-GAL titers of 1:50 or greater to receive two intratumoral α-gal glycolipid injections spaced 4 weeks apart. Patients were grouped into three cohorts, with three patients in each. Cohort 1 received 0.1 mg/injections; cohort II, 1.0 mg/injections; and cohort III, 10 mg/injections.
Dr. Albertini and fellow researchers assessed treatment outcomes 8 weeks post-injection, and found mild injection-site toxicity, and no systemic toxicity or autoimmunity. According to RECIST criteria, two patients had stable disease lasting 8 and 7 months. Minimal to no changes were seen in inflammatory infiltrate upon tumor nodule biopsies conducted pre- and post-treatment, with the exception of one patient in cohort III, who had a post-treatment inflammatory infiltrate.
At 2 and 4 weeks after injection, the treated nodules in five patients demonstrated tumor cell necrosis, with no neutrophilic or lymphocytic inflammatory responses. In 2 of 4 patients, non-treated tumor nodules showed necrosis as well.
The development of a synthetic version of the alpha-gal glycolipids is now underway, and, based on these results, Dr. Albertini has plans to further study this approach, possibly in tandem with the newer immunotherapy drugs currently available but to which not all patients respond.