Gangliosides as therapeutic targets for cancer.
Gangliosides, sialic acid-containing glycosphingolipids, have engendered great interest for more than 20 years in the search for target molecules of relevance for tumour growth and formation of metastases and as potential targets for immunotherapy. These molecules show large quantitative and structural variability, which is related to cell type and developmental stage. Their potential role in the formation of tumour metastases was suggested from data supporting that they are involved in cell growth regulation and in cell-cell and cell-matrix adhesion. Moreover, gangliosides are expressed on the cell surface and thereby are accessible for antibodies or other ganglioside-binding molecules to induce cell death, inhibit cell growth and/or inhibit formation of tumour metastasis. All tumours exhibit aberrant ganglioside expression. This includes overexpression of normal ganglioside constituents, which appears to be common among various tumours, and expression of gangliosides not found in normal adult tissue but often found during fetal development. The ganglioside composition of melanoma cells has been found to correlate with their metastatic potential and also to be selectively expressed in cells of a tumour mass and invading tumour cells. Passive immunotherapy using murine or murine/human chimeric monoclonal antiganglioside antibodies in their native form or combined with various effector molecules has been investigated. However, the vaccination strategy using native or structurally modified tumour-associated gangliosides in combination with adjuvants is currently the dominant method in clinical trials. The outcomes reported so far vary between type of tumour and treatment strategies. However, we believe that targeting gangliosides is as promising as any other immune therapeutic strategy, and basic research as well as clinical trials utilising new aspects is encouraged.
Experimental Neuroscience Section, Institute of Clinical Neuroscience, The Sahlgrenska Institute at Göteborg University, Sahlgrenska University Hospital, SE 43180 Molndal, Sweden. Pam.Fredman@neuro.gu.se
Pam
P
Fredman
Kristina
K
Hedberg
Thomas
T
Brezicka
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005732:Gangliosides / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D005732:Gangliosides