Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer

Table S2. Change in NK population in PBL

Additional file 1: of Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer

Table S1. Summary of NK cell expansion from 31 cancer patients (supplementary information of reference #25)

Phase I Clinical Trial of Fibronectin CH296-Stimulated T Cell Therapy in Patients with Advanced Cancer

<div><p>Background</p><p>Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT) and that fibronectin CH296 (FN-CH296) together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer.</p><p>Methods</p><p>Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up.</p><p>Results</p><p>Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%.</p><p>Conclusions</p><p>The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies.</p><p>Trial Registration</p><p>UMIN <a href="https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000002101&language=J" target="_blank">UMIN000001835</a></p></div

Tumor response.

<p>CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; 95% CI = 95% confidence interval.</p

Characteristics of infused cells.

<p>Patient no. 1 to 6 needed a one-time culture and patients 7 to 9 underewent three lymphocyte cultures.</p><p>Values are expressed as mean±SD.</p

Treatment protocol.

<p>Subjects received CH296-stimulated T-cell therapy on days 1 and 15. We conducted safety evaluations for the first 6 weeks of treatment. Patients who wished to continue the treatment received up to 4 further treatments every 2 weeks. To test immune function, venous blood was obtained from subjects before the start of therapy (baseline) and during follow-up one which occurred at 4 weeks (2 treatments) and after 6 cultured cell administrations.</p

Longitudinal plots of whole blood cytokine levels plotted according to the deviation of cytokine levels from the baseline.

<p>Mean cytokine levels in subjects in each cohort (A) and levels for the various tumor responses (B) are shown.</p