Abstract 4998: Development of a personalized off-the-shelf whole-cell immunotherapy for breast cancer

Abstract

BACKGROUND: Whole-cell cancer immunotherapies induce cancer-specific immune responses with the goal of long-term immune surveillance and remission. Non-replicating (irradiated) cancer cells are used to stimulate the immune system to recognize tumor-associated antigens and target tumor cells. Whole-cell immunotherapies have achieved regression of bulky, macroscopic tumors, but clinical trials have shown limited efficacy. SV-BR-1-GM is an HLA class I and II expressing, GM-CSF secreting breast cancer cell line. In a pilot clinical trial, an almost complete response of widely metastatic breast cancer was seen in a patient who allele-matched SV-BR-1-GM at HLA-DRB3. A follow-up Phase I/IIa clinical trial is ongoing in subjects with advanced breast cancer. RESULTS: Extensive in vitro analysis demonstrated that SV-BR-1-GM cells not only have features of breast cancer cells but surprisingly also features of dendritic cells, the latter especially because of the expression of both HLA class I and class II complexes. SV-BR-1-GM cells “loaded” with a peptide known to bind to histocompatibility complexes containing HLA-DRβ3, as allele-encoded by SV-BR-1-GM, induced the activation of a CD4+ T cell clone specific for the peptide-DRβ3 complex, suggesting functionality of SV-BR-1-GM’s HLA II machinery. To date, 24 subjects have been inoculated with the SV-BR-1-GM regimen in a Phase I/IIa trial with no adverse immediate hypersensitivity responses to low-dose inoculations with test cells (SV-BR-1 or SV-BR-1-GM). DTH response was evaluable in 18 patients with 72% developing DTH. The patient with the most pronounced DTH response, 01-002, also had a clinical response with regression of 20 of 20 lung metastases. Two other patients also had evidence of tumor regression. 6 patients were assessed for anti-SV-BR-1 antibodies. Whereas antibodies were found in sera of all patients, higher titers were measured in post-treatment compared to baseline samples. Patients who responded to the SV-BR-1-GM regimen with tumor regression matched SV-BR-1-GM at least at one HLA allele. CONCLUSIONS AND OUTLOOK: SV-BR-1-GM cells may act as antigen-presenting cells directly activating HLA matching patient T cells. To include more patients predicted to derive clinical benefit from this whole-cell approach, SV-BR-1 cells are being engineered to, among others, overexpress exogenous HLA alleles. The goal is to develop a set of cell lines suitable for personalized off-the-shelf immunotherapy. The strategy will result in cell lines that match ~90% of the US population at 2 or more HLA alleles. Citation Format: Vivekananda (Vivek) Sunkari, Sanne Graeve, George E. Peoples, Charles L. Wiseman, William V. Williams, Markus D. Lacher. Development of a personalized off-the-shelf whole-cell immunotherapy for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4998.