Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

Abstract

ABSTRACT1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to an Ab1 MAb which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some human tumors. Preparations containing this Ab2 were capable to induce a strong anti-metastatic effect in tumor-bearing mice. We conducted a Phase I clinical trial to evaluate the toxicity and humoral immune response elicited by 1E10 vaccine in patients with small cell lung cancer (SCLC). Eligible patients were those who after received chemotherapy and/or radiotherapy had partial or complete response to treatment. Patients received four biweekly injections with 2 mg of aluminum hydroxide-precipitated 1E10 MAb, then other six doses at 28-day intervals, and later the patients who maintained a good performance status were reimmunized. Six patients with limited-stage disease and three with extensive-stage disease were enrolled in the study. Most of the patients who received at least four doses of 1E10 vaccine developed strong specific antibody responses against 1E10 MAb and NeuGc-GM3 ganglioside. Antibodies able to react with lung carcinoma tissue sections were detected in sera from vaccinated patients. A prolonged survival was observed in several patients treated with the anti-idiotype vaccine. No evidence of serious adverse effects was found.

Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody

“…Thirteen patients received more than 10 doses of the anti-Id mAb, and confirmation of the safety of the treatment with this anti-Id vaccine preparation was reported in the previous clinical trials (21,26,27). The treatment of NSCLC patients with 1E10 mAb elicited Abs that shared the capacity of P3 mAb to recognize NeuGcGM3.…”

A Randomized, Multicenter, Placebo-Controlled Clinical Trial of Racotumomab-Alum Vaccine as Switch Maintenance Therapy in Advanced Non–Small Cell Lung Cancer Patients

“…This Ab2, named 1E10 and later racotumomab (26), was generated from immunizing BALB/c mice with P3 mAb, an Ab1 antibody that recognizes NeuGc gangliosides (27)(28)(29)(30). Racotumomab vaccine was able to generate a strong antitumor activity in mice bearing melanoma or breast carcinomas (26) and to induce antimetastatic effect in 3LL-D122 Lewis Lung carcinoma, a poorly immunogenic and highly metastatic murine model in C57BL/6 mice.…”

Lonely killers

“…[58][59][60][61]63 A positive correlation between the development of such antibodies and patient survival was found. 63 Despite the lack of direct cytotoxicity by P3 mAb, 66 the antibodies generated by the anti-idiotypic vaccine were able to directly kill GM3(Neu5Gc)-expressing cells.…”

“…GM3(Neu5Gc) is a ganglioside whose expression has been detected in some human tumors, including breast and melanoma. 53,55,56 Several therapeutic strategies have been developed against this target, 14 e.g., vaccines (ganglioside-based 57 and antiidiotypic [58][59][60][61][62][63] ) and mAbs. 55 14F7 mAb is specific for this ganglioside and unable to bind its N-acetylated (Neu5Ac) counterpart.…”