CAPRI culture supernatants should clarify whether CD4+ T lymphocytes only provide cytokine help to cytotoxic CD8+ T cells. Supernatants were added at depletion time point 1) or 2). In the absence of CD4+ T cells, cancer cells were only minimally destroyed (not shown). Several reports have described the suppression of cytolytic responses against human cancer cells by CD4+CD25+ regulatory T cells [37–45]. Modulation and suppression have appeared to be restricted to CD4+CD25highFoxp3+ T lymphocytes, either antigen-specific or non-antigen-specific [37–45]. The percentage of CD4+CD25highFoxp3+ T lymphocytes is strongly increased in CD3-activated cells BMN 673 compared to unstimulated

PBMC. In CAPRI cultures, this increase is only moderate (Fig. 6). Breast cancer cells were implanted in twelve

female mice. After tumour implantation, six mice were injected with autologous PBMC (controls), and the other six were injected with autologous CAPRI cells (verum). In this breast cancer model, the average tumour size was 29.64 ± 6.95 mm in the control group, whereas the tumour size was 5.08 ± 1.66 mm in the mice receiving CAPRI cell therapy. Furthermore, the verum group showed an average survival time of 43 ± 1.17 days, and the control group survived an average of 29.67 ± 1.92 days (P = 5.06 × 10−4, Fig. 7A, C, D, Table 2). Breast cancer patients (T1-4N0-2M1, G2-3) treated with CAPRI cells in an adjuvant treatment attempt were compared with patients of the Munich Dabrafenib Tumor Center (T1-4N0-2M1, G2-3) using Kaplan–Meyer statistics. All breast cancer patients with distant metastasis who received at least 500 × 106 CAPRI cells in total were included in the comparative analysis. It was recommended that patients should receive 60–80 × 106 CAPRI cells thrice a week for at least 1 year. Despite variations in the frequency of injection and cell number, which are unavoidable in treatment attempts, CAPRI cell-treated patients showed a significant increase in survival (Fig. 7B). Patients reported no adverse reactions PAK6 from CAPRI cells; rather, adverse reactions from chemotherapy were neutralized

by the CAPRI cell therapy. Most patients with adjuvant CAPRI cell treatment were able to resume professional activities 1 day after chemotherapy. The dramatic power of autologous MHC-restricted immune responses, first recognized by Zinkernagel and Doherty [46], contrasts with the immune surveillance failure of MHC-restricted tumour-infiltrating lymphocytes (TIL). However, TIL can be successfully revived in vitro [47]. ACT using autologous TIL combined with non-myeloablative chemotherapy and irradiation achieved a complete response in seven of 25 patients (28%) [47], a fundamental progress for ACT. Unprofessional presentation of tumour-immunogenic peptides and costimulatory molecules by cancer cells often induces the inactivation of naïve T cells.