Preliminary Safety and Potential Effect of 6B11-OCIK Adoptive Cell Therapy Against Platinum-Resistant Recurrent or Refractory Ovarian Cancer

Abstract

Ovarian cancer is a leading cause of death among gynecological malignancies, and novel therapies are urgently needed. Here we report preliminary findings on the potential safety and efficacy of 6B11-OCIK, an adoptive cell therapy of autologous T cells induced by the humanized anti-idiotypic antibody 6B11 minibody plus dendritic cells and cytokines, against platinum-resistant recurrent or refractory ovarian cancer in three patients. We found that 6B11-OCIK treatment was safe and well tolerated after five cycles of intravenous infusion with an initial dose of 1–2×109 cells and a dose-climbing strategy. Hemoglobin, platelets, white cell count, creatinine or liver enzyme values, coagulation function, kidney and heart function were not significantly affected over the duration of therapy. Two of the three enrolled patients showed potentially drug-related grade 1 and 2 weakness, and no other adverse events were observed. Of the three enrolled patients, one had stable disease and two showed disease progression. The patient with favorable clinical efficacy had better immune response as measured by 6B11-OCIK proliferation capacity, activation ability of CD3+CD8+ tumor-specific cytotoxic T lymphocytes and CD3+CD56+ cytokine-induced killer cells, and tumor cell killing efficiency. Changes in circulating tumor cells after treatment were consistent with serum level CA125 in the patient with stable disease (both decreased), while differences were observed in the two patients with disease progression (increased CA125 in both and decreased CTC in the patient with better immune response), suggesting that variation of circulating tumor cells was more consistent with immune response and reflected efficacy directly. This preliminary study suggested that autologous 6B11-OCIK treatment was safe and had potential clinical efficacy against ovarian cancer. Patients with better immune response had more favorable efficacy. In addition to imaging, CA125 and immunophenotypes, CTC monitoring may represent a potential indicator of immunotherapy response.

PRKDC-Mediated NHEJ May Play a Crucial Role in Aneuploidy of Chromosome 8-Driven Progression of Ovarian Cancer

“…Importantly, CTCs carry all or part of the genetic information of the primary tumor, which has made CTCs critical diagnostic markers and/or sources for tumor evaluation that aid in precision medicine. In our previous study, we used the SE-iFISH system with probes for CEP8 and CA125 or HE4 expression to identify CTCs [23]. This system is convenient for detecting the aneuploidy of Chr8, and the results indicated that among the 210 CTCs from 20 EOC patients, almost all CTCs showed Chr8 aneuploidy, which was consistent with single-cell sequencing and TCGA analysis.…”

“…We defined c-Myc amplification as ≥1.5 copies of c-Myc/CEP8 per cell and found that c-Myc amplification was associated with the pathological pattern, grade, lymphatic metastasis, and ER positivity (Table 3). Circulating tumor cells (CTCs) in peripheral blood were enriched by SE-iFISH, as described in our previous study [23]. A total of 210 CTCs were enriched from 20 EOC patients.…”

“…The detailed method and screening cohort were shown in our previous research [23,24]. Briefly, the SE-iFISH system was used to identify circulating tumor cells.…”

Metabolic reprogramming of the tumor immune microenvironment in ovarian cancer: A novel orientation for immunotherapy

“…It can be helpful to improve the immune escape of ovarian cancer, especially for patients with recurrent ovarian cancer. An adoptive cell therapy of autologous T cells induced by a humanized anti-adiotypic antibody 6B11 minibody plus DCs and cytokines demonstrated preliminary safety and potential clinical efficacy in a phase I clinical trial of platinum-resistant recurrent or refractory ovarian cancer (144). A phase II study of allogeneic NK cell therapy for recurrent ovarian cancer showed suboptimal efficacy, and Treg cells were revealed to represent a treatment barrier (157).…”