Vaccines have been studied in many types of cancer but unfortunately not always successfully. This time the data look very promising. The new data showed that vaccination might play a role in colorectal cancer. I was very interested in reading about it in March’s ASCO Post because the principal investigator (PI), Martin Scurr from Cardiff University in the UK who initiated the study called TaCTiCC to test a specific type of vaccine targeting cancer cells is a PhD scientist. It is nice to see when PhD scientists get special recognition for taking responsibility in an innovative clinical program and presenting the data at conferences like the ASCO-SITC 2017 (Society for Immunotherapy of Cancer).
The vaccine used in the study represents a tumor-associated antigen called 5T4 that is found in a wide range of solid cancers including up to 90% of colorectal tumors. Therefore, other tumors with frequent 5T4 expression could be treated with the here described vaccine as well. In fact the vaccine is currently evaluated in a number of tumor types.
The study had an open label, randomized P1/2 design with 4 arms: No treatment vs low dose of the chemotherapeutic cyclophosphamide vs vaccine alone vs low dose cyclophosaphamide and the vaccine combined.
Immunotherapeutics are not always effective in patients due to the presence of regulatory T cells (Tregs). This is one caveat in immunotherapy like vaccination and also checkpoint inhibition. Low dose cyclophosphamide has been shown to downregulate Tregs. That’s why it has been chosen for this study. The study aimed to prove that the combination is able to deplete Tregs defined as Foxp3-positive CD4-positive T cells. The results of the study showed that the three treatment arms did induce an immune response compared with the no treatment arm. Furthermore, the PI presented improvements in progression free and overall survival, which of course needs to be prospectively confirmed with larger patient numbers. However, the combination did not boost the response significantly over the two mono-therapy arms. This could be explained by several factors such as that the schedule needs to be adjusted, concentration titrated and/or the regimen needs to be tested earlier in the treatment algorithm of CRC patients. The TaCTiCC trial enrolled end-stage patients that are most likely heavily pre-treated.
One very important result of this study is that not providing the patient with any type of therapy has the lowest clinical outcome, which may be done with some patients with end-stage CRC. The remaining options for them are currently palliative chemotherapy or best supportive care. Hopefully, Dr. Scurr will continue to show silver linings for these fatally ill patients.
The ASCO Post Volume 8 Issues March 25 2017: Novel Immunotherapeutic Vaccine Studied in Colorectal Cancer by Caroline Helwick.