Cancer Vaccines in Ovarian Cancer: How Can We Improve?

Abstract

Epithelial ovarian cancer (EOC) is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago) but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC) vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials.

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

“…Vaccine-induced immune responses provide long-term immunologic memory. Cancer vaccines may be classified into cell-based vaccines, peptide/protein vaccines, epigenetic vaccines, and genetic vaccines ( 82 ). Among these, peptide/protein vaccines and cell-based vaccines are usually based on well-defined TAAs ( 51 ).…”

Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

“…In addition to the use of bacteria and oncolytic viruses, which effectively behave as in situ vaccines and stimulate the immune system without the need for isolation and identification of antigens [ 261 ], a variety of therapeutic cancer vaccine platforms have been developed and tested. A therapeutic vaccine should be able to induce cell mediated immunity in which immune cells are activated to recognise and destroy their cellular targets in affected tissue [ 269 ]. Cancer vaccines include: (1) whole tumour cell vaccines, based on the administration of cancer cell lysates; (2) peptide-based vaccines, based on the direct delivery of recombinant proteins or epitopes in combination with immunological adjuvants; (3) dendritic cell (DC)-based vaccines, most often based on the isolation of patient-derived DCs, matured ex vivo in the presence of TAAs and their re-infusion; (4) RNA-based vaccines, based on the direct delivery of RNA molecules extracted from malignant cells or specifically encoding a single TAA; (5) DNA-based vaccines, based on the administration of naked plasmids or vectored TAA-coding plasmids under the control of a strong mammalian or viral promoter [ 270 ].…”

“…A number of ovarian cancer trials have been conducted in patients using vaccinations with ESO 157-170, a short peptide of the CTA NY-ESO-1 [ 271 ], and heterologous prime-boost vaccinations [ 6 ], i.e., multiple vaccinations with different delivery vectors encoding the same recombinant antigen [ 272 ]. Generally, therapeutic cancer vaccines are associated with minimal side effects, but they have shown consistently low efficacy [ 269 ].…”

“…A more recent study included five recurrent ovarian cancer patients with DCs loaded with hypochlorous acid-oxidized whole tumour lysate (to induce primary necrosis and enhance the immunogenicity of lysed tumour cells), administered into the regional lymph node (intranodally). Two patients had a durable progression-free survival for two years or more [ 269 ]. Cancer vaccines, including DC vaccines, however, have been criticised for their low therapeutic efficacy, so it is thought that combining them with other immunomodulatory agents such as immune checkpoint inhibitors, IDO1 inhibitors, Ontak, and other intervention strategies may improve patient outcomes [ 269 ].…”

“…Two patients had a durable progression-free survival for two years or more [ 269 ]. Cancer vaccines, including DC vaccines, however, have been criticised for their low therapeutic efficacy, so it is thought that combining them with other immunomodulatory agents such as immune checkpoint inhibitors, IDO1 inhibitors, Ontak, and other intervention strategies may improve patient outcomes [ 269 ]. Allogeneic DC vaccines [ 261 ] and DC-derived exosomes [ 351 ] have been trialled for some cancers, though to date not ovarian cancer.…”