Cervical cancer is the fourth most common
cancer in women with an estimated 570,000 new cases in 2018 which constitute about 6. 6% of all
cancers in women according to WHO report 2018. Approximately 90% of the 270,000 deaths from
cervical cancer in 2015 occurred in low- and middle-income countries. In
cervical cancers, which is caused by human papillomavirus (HPV)
infection, the expression of HPV 16 E6 and E7
proteins are essential for
tumor cell transformation and maintenance of
malignancy. Prophylactic
vaccines against
cervical cancer caused by human papillomavirus have not proven successful. Although virus-like particle-based (VLPs)
vaccines have been developed with prophylactic activities to prevent most
HPV infections, the
therapeutic effect of VLP
vaccines has yet to be demonstrated for those who were already infected. A recent study showed that pre-conditioning mice with a potent
antigen such as
tetanus toxoid significantly improves lymph node homing and efficacy of dendritic cells.
Tetanus toxoid has also been used in combination with
DNA vaccines designed from
tumor based
antigens. In the present study, we pre-conditioned mice with
tetanus toxoid followed by vaccination with a
Granulocyte-Macrophage Colony-Stimulating Factor (
GM-CSF) overexpressing
tumor-cell based
vaccine (GVAX). We observed that pre-conditioning with
tetanus toxoid followed by vaccination with GVAX regressed
tumor growth and enhanced the overall survival of the mice. Pre-conditioning with
tetanus toxoid enhanced the immune response which was observed by
enlarged spleen size, higher proliferation rate of lymphocytes, a higher level of IFN-γ, TNF-α, and
IL-4 antigen-specific secretions by the splenocytes. Pre-conditioning with
tetanus toxoid increased memory T cell migration into the
tumor site and spleen. The
antigen-specific cytotoxic T cell lysis percentage was also found to be higher in the group of mice vaccinated with the combination of
tetanus toxoid and GVAX. Hence, pre-conditioning with
tetanus toxoid prior to vaccination with a
tumor-cell based
vaccine overexpressing
GM-CSF might be an effective strategy for targeting E7-specific HPV-associated cervical
malignancy.