Strong vaccine responses during chemotherapy are associated with prolonged cancer survival.
Cornelis J M MeliefMarij J P WeltersIgnace VergoteJudith R KroepGemma G KenterPetronella B OttevangerWiebren A A TjalmaHannelore DenysMariette I E van PoelgeestHans W NijmanAnna K L ReynersThierry VeluFrederic GoffinRoy I LalisangNikki M LoofSanne BoekestijnWillem Jan KrebberLeon HooftmanSonja VisscherBrent A BlumensteinRichard B SteadWinald R GerritsenSjoerd H Van der BurgPublished in: Science translational medicine (2021)
Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)-induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high numbers of immunosuppressive myeloid cells in patients, allowing the development of much stronger therapeutic HPV16 vaccine (ISA101)-induced tumor immunity. We now show the clinical effects of ISA101 vaccination during chemotherapy in 77 patients with advanced, recurrent, or metastatic cervical cancer in a dose assessment study of ISA101. Tumor regressions were observed in 43% of 72 evaluable patients. The depletion of myeloid suppressive cells by carboplatin/paclitaxel was associated with detection of low frequency of spontaneous HPV16-specific immunity in 21 of 62 tested patients. Patients mounted type 1 T cell responses to the vaccine across all doses. The group of patients with higher than median vaccine-induced immune responses lived longer, with a flat tail on the survival curve. This demonstrates that chemoimmunotherapy can be exploited to the benefit of patients with advanced cancer based on a defined mode of action.
Keyphrases
- end stage renal disease
- ejection fraction
- high glucose
- newly diagnosed
- chronic kidney disease
- prognostic factors
- squamous cell carcinoma
- high grade
- endothelial cells
- small cell lung cancer
- drug induced
- palliative care
- peritoneal dialysis
- young adults
- bone marrow
- inflammatory response
- clinical trial
- healthcare
- cell proliferation
- signaling pathway
- randomized controlled trial
- dendritic cells
- acute myeloid leukemia
- oxidative stress
- childhood cancer
- real time pcr
- chemotherapy induced
- squamous cell
- open label