Regression of cutaneous metastatic melanoma by intralesional injection with human monoclonal antibody to ganglioside GD2.

Abstract

In this study we used human monoclonal antibody (Hu-mAb) L72 as an intratumoral injection of cutaneous metastasis of melanoma to study its anti-tumor effects in human patients. Hu-mAb L72 was developed by transforming peripheral blood lymphocytes from a melanoma patient in vitro with the Epstein-Barr virus, forming a human lymphoblastoid cell line that produces 2-5 gig of IgM per ml. This IgM Hu-mAb was shown to react specifically with ganglioside GD2 and have a strong cytotoxic effect on human melanoma cells in the presence of complement. Patients with cutaneous metastatic melanoma were given intralesional injections on a daily or weekly injection schedule. Regression was seen in all tumors except in those of two patients whose tumors were shown to have low antigenicity. Histopathological data showed tumor degeneration, fibrosis, free melanin, and some degree of lymphocyte or macrophage infiltration. One patient with melanoma satellitosis treated with Hu-mAb showed complete regression with no sign of recurrence 20 months after the initial treatment. With the exception of mild erythema, no side effects were observed in any patient.

Endogenous immune response to gangliosides in patients with confined prostate cancer

“…GD2 is considered to be immunogenic in human cancers 41,44 and considered as a potential target for both passive [44][45][46] and active specific immunotherapies 47 of melanoma. Although we could not observe any significant difference in the anti-GD2 response among our study groups, we did not test the sera against O-acetylated GD2 only.…”

An Anti‐GD2 Monoclonal Antibody Enhances Apoptotic Effects of Anti‐cancer Drugs against Small Cell Lung Cancer Cells via JNK (c‐Jun Terminal Kinase) Activation

“…18) In particular, anti-ganglioside mAbs have been tried for immunotherapy of melanomas 19,20) and neuroblastomas.…”

“…22) Moreover, a human mAb reactive with GD2 was tried for cutaneous melanomas with some effects. 20) However, further development of antibody therapy has not been successful mainly due to xenogeneic immunogenicity of mouse antibodies and poor penetration of antibodies into tumor tissues.…”

“…Specific monoclonal antibodies (mAbs) to these tumor-associated ganglioside antigens have been utilized for diagnosis, 14,15) prediction of the prognosis, 16,17) and detection of residual tumors. 18) In particular, anti-ganglioside mAbs have been tried for immunotherapy of melanomas 19,20) and neuroblastomas. 21) During the early stage of mAb application, anti-GD3 mAb R24 was used for the first time in the treatment of recurrent melanomas, and showed the ability to reduce the tumor size or halt the progression.…”

Preparation and characterization of a chimeric CD 19 monoclonal antibody

“…e\'en in situations where the patient is profoundly iinniunosuppressed (6), The use of human monoclonal antibodies provides a possible solution. and at least one sueeessful clinical study has been reported (7). However, severe technical limitations in producing human monoclonal antibodies remain, and few have reached a stage where they can be considered for patient use.…”