Adoptive cell transfer therapy with ex vivo primed peripheral lymphocytes in combination with chemotherapy in locally advanced or metastatic triple-negative breast cancer: the ImmunoBreast phase Ib clinical trial.

backgroundAdoptive cell transfer-based immunotherapy holds promise for treating advanced cancer. However, a key challenge remains: generating sufficient numbers of lymphocytes capable of recognizing and targeting a broad range of cancer antigens. We recently developed Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT), a novel procedure for selecting, expanding and maturing polyclonal lymphocytes from peripheral blood with the capacity to target cancer cells. In this single-center phase Ib trial, we evaluated the safety, tolerability, and preliminary efficacy of ALECSAT in combination with standard carboplatin and gemcitabine in patients with locally advanced or metastatic triple-negative breast cancer (mTNBC).

methodsThis clinical study enrolled 15 patients with mTNBC. The patients received three ALECSAT doses, administered every 28 days. Subsequently, ALECSAT doses were given at 6-week intervals. Carboplatin and gemcitabine were administered on days 1 and 8 in 3-week cycles. The cell composition of ALECSAT preparations was analyzed using flow cytometry. Additionally, patient-derived xenograft (PDX) mouse models were generated and treated with ALECSAT to assess treatment responses.

results14 patients with mTNBC, who had received one to four prior treatment lines, were treated with 1-10 doses of ALECSAT. The combination of ALECSAT with carboplatin and gemcitabine was well tolerated and demonstrated a favorable safety profile. Common adverse events (AEs), including fatigue, nausea, and hematological abnormalities, were consistent with the known toxicity profiles of carboplatin and gemcitabine. Notably, grade ≥3 AEs were predominantly hematological, with manageable durations of neutropenia and thrombocytopenia. Among treated patients, one achieved a complete response, four had partial responses, five had stable disease, and four had progressive disease. The objective response rate was 36% (95% CI 12.8% to 64.9%). Median progression-free survival was 4.3 months (95% CI 1.6 to 7.0), while median overall survival was 8.7 months (95% CI 5.1 to 12.4). A positive correlation was observed between the total number of administered ALECSAT cells (particularly CD8+T cells) and time to progression. Additionally, ALECSAT treatment outcomes in patients correlated with responses observed in their corresponding PDX models.

conclusionALECSAT, in combination with carboplatin and gemcitabine, was safe, well tolerated, and demonstrated promising antitumor activity in mTNBC. These findings support further investigation in larger clinical trials. TRIAL REGISTRATION NUMBER: NCT00891345.