Recombinant DNA Technology for Melanoma Immunotherapy: Anti-Id DNA Vaccines Targeting High Molecular Weight Melanoma-Associated Antigen

Abstract

Anti-idiotypic MK2-23 monoclonal antibody (anti-Id MK2-23 mAb), which mimics the high molecular weight melanoma-associated antigen (HMW-MAA), has been used to implement active immunotherapy against melanoma. However, due to safety and standardization issues, this approach never entered extensive clinical trials. In the present study, we investigated the usage of DNA vaccines as an alternative to MK2-23 mAb immunization. MK2-23 DNA plasmids coding for single chain (scFv) MK2-23 antibody were constructed via the insertion of variable heavy (V H) and light (V L) chains of MK2-23 into the pVAC-1mcs plasmids. Two alternative MK2-23 plasmids format V H/V L, and V L/V H were assembled. We demonstrate that both polypeptides expressed by scFv plasmids in vitro retained the ability to mimic HMW-MAA antigen, and to elicit specific anti-HMW-MAA humoral and cellular immunoresponses in immunized mice. Notably, MK2-23 scFv DNA vaccines impaired the onset and growth of transplantable B16 melanoma cells not engineered to express HMW-MAA. This pilot study suggests that optimized MK2-23 scFv DNA vaccines could potentially provide a safer and cost-effective alternative to anti-Id antibody immunization, for melanoma immunotherapy.

Chondroitin Sulfate Proteoglycan 4 and Its Potential As an Antibody Immunotherapy Target across Different Tumor Types

“…Despite the promising clinical results, MK2-23 never reached clinical application as a therapy due to standardization issues and safety concerns linked to its administration together with the adjuvant Bacille Calmette-Guerin (BCG), deemed necessary for triggering effective adaptive immune responses ( 94 ). Further approaches to overcome those issues included fusing MK2-23 to human IL-2 ( 94 ) or utilizing DNA vaccines encoding MK2-23 scFv ( 95 ). In a phase I clinical trial, another anti-idiotypic antibody, MF11-30, induced complete remission in one advanced melanoma patient as well as conferred minor survival benefits in three other patients with advanced melanoma whilst no toxicities were reported as a part of Ref.…”

Chondroitin sulfate proteoglycan 4: An attractive target for antibody-based immunotherapy

“…59) Attempts to address these concerns involved fusing MK2-23 with human IL-2 59) or creating deoxyribonucleic acid (DNA) vaccines that encode MK2-23 scFv. 60) In 1990, Mittelman et al 61) presented their findings from two clinical trials on the use of the mouse-derived mAb, MF11-30, for treating stage IV malignant melanoma. This mAb, which mimics human HMW-MAA, was administered to patients subcutaneously at varying doses.…”

Strategies in DNA vaccine for melanoma cancer

“…The human high molecular weight melanoma-associated antigen (HMW-MAA) is a cell surface proteoglycan expressed in more than immunization (Barucca et al, 2014). It has been also shown that the plasmid DNA vaccine encoding for streptococcus pyogenes EMM55 protein (pAc/emm55) could increase the IgG antibodies and immune responses in horses with metastatic melanoma.…”