Colorectal
Ankur Tiwari, MBBS
Resident
University of Texas Health Science Center San Antonio, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Increased CD8+ tumor infiltrating leukocytes (TILs) and a decreased ratio of CD4:CD8 TILs are associated with a better prognosis in colon cancer. A vaccine that can lead to these changes may be more likely to have clinical benefit. The PalloV-CC (particle-delivered, allogeneic tumor cell lysate vaccine for colon cancer) vaccine utilizes silicate-capped yeast cell wall particles to deliver allogenic colon cancer tumor lysate. Here we present the first-in-human results from a phase I neoadjuvant window trial looking at effects of the vaccine on the tumor immune microenvironment.
Methods:
This is a single arm, phase I, open label study evaluating the effects of neoadjuvant vaccination with PalloV-CC on TIL levels. Patients with a new diagnosis of colon cancer on endoscopic biopsy, who were candidates for elective colectomy, were prospectively enrolled and vaccinated with Pallo-V-CC weekly for 4 weeks prior to surgery. The pre- and post-treatment tissue was evaluated for the quantification of CD4+ and CD8+ TILs by immunohistochemistry and compared with a paired t-test.
Results:
15 patients were enrolled. Mean age of the participants was 60±3.8 yrs. Most common site of malignancy was the sigmoid colon (8/15, 53%). Four patients (27%) reported adverse events from the vaccine, that were limited to grade 1 or 2 toxicities. There were no reported surgical complications. Paired tissue samples were available for 7 patients. Quantification of CD4+ and CD8+ lymphocytes revealed a non-statistically significant increase in mean CD8+ TIL in post-treatment samples (85.0 ± 28.1 cells/mm3) compared to pre-treatment (55.8 ± 13.1 cells/mm3; p=0.37). CD4+ TIL decreased with treatment, though again, the change did not meet statistical significance (222.6 ± 48.4 to 112.7 ± 25.1 cells/mm3, p=0.14). The CD4:CD8 ratio within the tumor decreased with treatment (5.1 ± 1.6 to 2.5 ± 0.7, p=0.21).
Conclusions:
The PalloV-CC vaccine is safe with minimal adverse events. An increase in CD8+ TIL and decreased CD4:CD8 ratio was observed with neoadjuvant administration, although a larger sample size is needed to confirm this finding.