The Academy

By Matthew Mahady
Published: Wednesday, Jun 09, 2010
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University of Alabama, Birmingham

Second-Generation Monoclonal Antibody Demonstrates Benefit in Treatment-Resistant Follicular Lymphoma

Results from early-stage, preliminary (phase I) data presented by a team of University of Alabama researchers suggests that a second-generation, highly targeted monoclonal antibody may offer new hope for patients with follicular lymphoma (a particularly difficult to treat subtype of non-Hodgkin’s lymphoma) who have failed other treatments.

In all, 22 immune-cell variant patients have enrolled in the study and received regular treatment with the experimental agent AME-133v. Of the participants, 20 had received unsuccessful prior treatment with rituximab (Rituxan) and 19 had also had chemotherapy. For the dose escalation phase of the study, 20 of the 22 participating patients were eligible to be evaluated. Researchers reported that the agent was well tolerated at all dosages. Only two (10%) participants reported anything beyond minor (grade I) adverse events. For the interim analysis of clinical benefit, 16 of the 22 subjects were evaluable. Of 16 patients that have been analyzed so far, four (25%) have attained either a partial response (PR) or a complete response (CR) to the novel therapy AME- 133v. Two of the four responding subjects demonstrated PR and two showed CR.

Commenting on the results, Andres Forero, MD, the study’s lead investigator, University of Alabama, Birmingham, Comprehensive Cancer Center, stated, “These first results suggest that AME- 133v provides a mechanism of action that may be more potent and ultimately more effective than the treatments we have on hand for a subset of patients with this cancer (who demonstrate immune cell variation or mutation). Monoclonal antibodies were the first successful targeted therapy for cancer, and we have now moved on to a whole new class of second-generation antibodies for the treatment of many different lymphomas. This is an exciting time.”

According to Dr. Forero, the interim results are robust enough to warrant continued study. “Given these encouraging (phase I) results, patients are currently being enrolled in a phase II study,” he reported.

The majority of patients in the study (20 of 22) either did not initially respond to—or relapsed after—the use of rituximab, the first monoclonal antibody therapy approved for use in lympho- ma treatment. AME-133v is a second-generation therapy that is believed to be a more specific treatment for follicular lymphoma in general, compared with rituximab, but is also thought to offer particular benefits for those patients who have a variant in the immune cells needed to attack the cancer.

Although treatment with rituximab as a single agent has resulted in significant responses in patients with almost every subtype of B-cell lymphoma, including follicular lymphoma, recent evidence has shown that some patients with effector immune cells that carry a mutation in the receptor protein FcγRIIIa 158-F do not have the same response. This is an issue that is related to the patient’s own biological makeup, not to the cancer cells themselves, he adds. There are three different classes of Fcγ receptors to which the monoclonal antibody binds on leukocyte effector cells—T helper cells—that direct other immune cells to the antigen. Response to rituximab depends on variants in the receptors these helper cells use.

AME-133v is an anti-CD20 antibody engineered to bind more strongly to these variant receptors. In preclinical studies, it demonstrated a 10-fold improvement in killing power of human B cells, compared with rituximab, researchers reported.

“AME-133v appears to be capable of binding with high specificity to cell-surface antigens, resulting in targeted killing of malignant cells, relative sparing of normal tissues, and low toxicity,” Dr. Forero concluded.

The data were presented during a recent poster session at the annual meeting of the American Association for Cancer Research in San Diego.

University of Buffalo

Gum Disease and Human Papillomavirus Linked to Tongue Cancer

The presence of gum disease in conjunction with human papillomavirus (HPV) can markedly increase tongue cancer risk, according to a new study conducted by researchers at the University at Buffalo School of Dental Medicine.

Previous studies have found that periodontitis, which destroys connective tissue and bone supporting the teeth, and HPV, each pose increased risks of cancer in the head, neck or tongue. The University of Buffalo research, however, is the first to suggest that the two conditions may work in tandem.

In a study of 30 patients newly diagnosed with squamous cell carcinoma on the base of the tongue, 63% (19 patients) had tumors testing positive for a common type of HPV. In addition, 90% of the patients with HPV-positive tumors had periodontitis, and 79% of patients whose tumors showed no presence of HPV did not have periodontitis.

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