Undoubtedly, vaccines are one of the most significant milestone inventions in mankind’s fight against diseases, and they have also played an essential role in the treatment of cancer.
If we say PD-1/PD-L1 inhibitors are the first “trump card” of immunotherapy, and adoptive cellular immunotherapy the second “trump card”, then tumor vaccines are undoubtedly the third “trump card” of immunotherapy. And it is also what I will introduce to you today: a tumor vaccine called GP2, which has led to a zero five-year recurrence rate in breast cancer patients and can be said to have cured them clinically.
Zero recurrences in the five-year follow-up: the emerging tumor vaccine brings hope of cure
The GP2 vaccine is a nine amino-acid transmembrane peptide derived from the HER2/neu protein. HER2/neu is a cell surface receptor protein, expressed in 75% of breast cancers and other common cancers. And GP2 can train patients’ T cells to recognize and destroy HER2/neu-expressing cancer cells and avoid recurrence.
The related trial enrolled a total of 168 patients, with the primary objective of determining whether the GP2 vaccine could reduce the recurrence rate of breast cancer in combination with the FDA-approved immune adjuvant GM-CSF. The study included patients with operable HER2-positive breast cancer, who were randomized to receive GP2 + GM-CSF and GM-CSF alone after the operation.
According to the study results:
After five years of follow-up, 46 HER2-positive patients who received GP2+GM-CSF treatment had a five-year disease-free survival (DFS) rate of 100% and none had a recurrence, while 50 patients who received GM-CSF treatment had a five-year DFS rate of 89.4% (95% CI: 76.2, 95.5%) (p=0.0338).
GP2 was shown to be well tolerated with no SAEs (serious adverse events) and elicited a potent immune response measured by local skin tests and immunological assays, which suggested peak immunity was reached at six months upon completion of treatment.
In other words, during the five years of trial follow-up, not only did the patients have five years of DFS, but also all of them had no recurrence. Isn’t this the ideal endpoint for all cancer patients? Isn’t this the dawn of cure that all patients are dreaming of?
Besides the major breakthrough in the area of breast cancer, the development of “therapeutic vaccines” for cancers has bloomed all over the world in 2020, with vaccines for various cancers launched. Many hospital medical supply companies have done a lot to this achievement.
Head and neck cancer: the mRNA-4157 vaccine
As an mRNA vaccine developed by Moderna, the mRNA-4157 vaccine uses a novel and gene-based technology, and is designed by comparing patients’ normal cell DNA sequence to that of their tumor, and identifying tumor specific changes to the DNA. By combining with pembrolizumab (a PD-1 inhibitor), researchers hypothesized that the vaccine could prime the immune system to be more responsive to the PD-1 inhibitor and reduce the risk of cancer recurrence.
Moderna announced the ability of mRNA-4157 in combination with Keytruda to shrink multiple advanced solid tumor foci on Nov. 11, 2020.
In 10 patients with HPV-negative head and neck squamous cell carcinoma, the overall response rate (ORR) reached 50%, with two patients achieving a complete response (CR) and three patients achieving a partial response (PR); four patients had stable disease, and the disease control rate (DCR) reached 90%.
The combination had a significant advantage over the use of the PD-1 inhibitor alone: the median progression-free survival (mPFS) reached 9.8 months.
The results were satisfactory even when the combination was compared with the Keytruda / chemo combination (standard of care for first-line treatment), which produced an ORR of 36% and an mPFS of 4.9 months.
This combined immunotherapy has been well tolerated so far, and the investigators plan to expand the study cohort to 40 patients, which means that 40 patients will receive a tailored mRNA vaccine that will stimulate the strongest immune response.
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