Abstract
Abstract Background: SV-BR-1-GM is a GM-CSF transfected breast cancer cell line, exceptional for having antigen-presenting capability and expressing both HLA I and II. The parent cell line, SV-BR-1, was derived from a patient with grade II (moderately differentiated) breast cancer. We report molecular characterization of SV-BR-1-GM, noting it retains features of a grade II tumor, and report enhanced disease control in patients with grade I or II breast cancer.Methods: SV-BR-1 and SV-BR-1-GM were characterized molecularly using RNAseq and proteomic analyses. We treated 23 evaluable patients with recurrent and/or metastatic breast cancer refractory to standard therapy. The SV-BR-1-GM regimen included cyclophosphamide 300 mg/m2 2-3d prior to intradermal injection of SV-BR-1-GM (20-40x106 cells divided into 4 sites) and IFNα into the inoculation sites (10,000 IU/site) about 48 and 96 hours subsequently. Cycles were q2 weeks x3 then qmo x 3 (clinical trial NCT03066947). Eleven patients were treated with the above regimen in combination with a PD-1 inhibitor (pembrolizumab or INCMGA00012) (clinical trial NCT03328026). Disease response was evaluated radiographically q3 mo and as clinically indicated. Results: To estimate the tumor grade represented by the SV-BR-1-GM cell line, we developed a score we refer to as Relative Molecular Grade (RMG). SV-BR-1-GM is most similar to the MDA-MB-468 cell line (RMG of 52.1), which was classified as Basal A phenotype. Basal A cancers are less aggressive than Basal B but more aggressive than Luminal, suggesting that SV-BR-1-GM may have retained features of a grade II breast cancer. We also noted that SV-BR-1-GM expresses both Class I (HLA-A, B & C) and Class II (HLA-DR and -DP) molecules, and that the HLA-DR expression is enhanced by treatment with IFNγ. SV-BR-1-GM expressed 31 genes which are overexpressed in breast cancer, 8 cancer-testis antigens and 3 genes expressed in breast tissue. In 30 patients treated with the SV-BR-1-GM regimen (19 with the SV-BR-1-GM regimen alone, 4 who began on the SV-BR-1-GM regimen and transitioned to combination with a PD-1i, and 7 with combination therapy alone) there were 7 with grade II breast cancer and 1 with grade I breast cancer (Table). These patients were heavily pre-treated with an average of 10 prior regimens. While only one patient with grade III cancer showed disease control, 75% of the patients with grade I or II tumors showed disease control. Patients remained on study for up to 259 days.Conclusions: SV-BR-1-GM appears to retain characteristics of a moderately differentiated breast cancer, expresses multiple potential tumor antigens, and can elicit disease control especially in patients with grade I and II breast cancer. TablePatients with Grade I/II TumorsCharacteristicSV-BR-1-GM Regimen Alone(n=6)SV-BR-1-GM Regimen + PD-1i(n=3)All Patients(n=8)Age64 ± 767 ± 465 ± 7Mean Prior Systemic Regimens6 (range 1-20)15 (range 14-15)10 (range 1-20)% ER/PR +80%100%86%% Her2/neu +0%33%14%% Triple Negative20%0%14%Delayed-type Hypersensitivity83%100%88%Disease Control Rate*67%100%75%Days on Study (Range)94 (32-181)189 (133-259)141 (32-259)•Includes CR, PR, SD (including minor responses and mixed responses) Citation Format: William Williams, Shaker R Dakhil, Carmen Calfa, Jarrod P Holmes, Saveri Bhattacharya, Jason Lukas, Elizabeth Tan-Chiu, George E Peoples, Vivek G Sunkari, Markus D Lacher, Charles L Wiseman. Response to a modified whole tumor cell targeted immunotherapy in patients with advanced breast cancer correlates with tumor grade [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-20.