Published Abstract Detailing Amazing, Unprecedented Response of HER2+ Breast Cancer Patients To AlloStim

Response of HER2+ breast cancer patients to allogeneic cell immunotherapy.

Meeting: 

2012 ASCO Annual Meeting

Abstract Number: 

e13013

Citation: 

J Clin Oncol 30, 2012 (suppl; abstr e13013)

 

Author(s): 

Michael Har-Noy, Wirote Lausoontornsiri, Reuven Or, Emmanual Katsanis; Immunovative Therapies, Ltd, Jerusalem, Israel; Clinical Cancer Research Department, National Cancer Institute of Thailand, Bangkok, Thailand; Hadassah Hebrew University Medical Center, Jerusalem, Israel; University of Arizona Medical Center, Tucson, AZ

 

Abstract: 
Background: The immune mechanism of non-myeloablative allogeneic stem cell transplantation has been shown to be effective in debulking chemotherapy-resistant metastatic cancer despite the presence of immunoavoidance mechanisms, but this immune effect is intimately related to GVHD toxicity limiting the clinical application. An allogeneic cell therapy (aCT) with intentionally mismatched, CD3/CD28 microbead-conjugated CD4+ memory cells exhibiting both Th1- and NK-like properties designed to elicit autologous anti-tumor effects in the context of graft rejection was evaluated in a FDA-approved phase I/II clinical trial of 42 refractory metastatic solid tumor patients with a variety of indications. No objective tumor response was observed, however there was evidence of enhanced survival and immune-mediated tumor debulking without GVHD toxicity. RECIST overestimated tumor burden, as responding tumors swelled and appeared larger on CT. Multi-parameter analysis identified serum IL-12 as a predictor of enhanced survival. 50% were IL-12+ and survived a median of 211 days vs. 131 days for IL-12- patients (p<.009). Methods: An analysis of IL-12+ responders was conducted to determine the indication with the highest IL-12 response. Results: 9 of 16 refractory metastatic breast cancer (mBC) patients were IL-12+. The Her2+ subset of mBC were 100% IL-12+ (5 of 5) with a median survival of 416 days, while the 11 Her2- patients had a median survival of only 134 days (p<0.05). Conclusions: Normally, Her2+ tumors are more aggressive and have a poorer prognosis than Her2- tumors. The enhanced response to aCT in Her2+ mBC may be due to high titers of anti-Her2 IgG1 antibodies known to be present in these patients. aCT upregulates host FcgR expression on host monocytes through a CD40L-CD40 mechanism. The FcgR bind IgG1 antibodies and mediate ADCC tumor lysis. We hypothesize that patients expressing tumor-specific IgG1 autoantibodies are more likely to respond to aCT. Serum autoantibodies to tumor-associated antigens thus may be a predictive biomarker for aCT responders. The combination of natural or exogenous tumor-specific IgG1 Abs with aCT may be a platform for refractory metastatic tumor debulking leading to increased overall survival.