What investigational vaccines show promise in cancer treatment?

Promising Investigational Cancer Vaccines

Several investigational vaccines targeting HPV-related antigens and other cancer mechanisms show significant promise in improving mortality and quality of life outcomes for cancer patients, particularly those with cervical cancer. 1

HPV-Targeting Vaccines for Cervical Cancer

HPV infection is strongly associated with cervical cancer development, making HPV-specific antigens excellent targets for therapeutic vaccination. The most promising investigational vaccines include:

Axalimogene Filolisbac (ADXS11-001)

• Live-attenuated E7-producing Listeria monocytogenes vaccine
• Has completed phase II trials with positive results
• Advanced to phase III clinical development
• Mechanism: Delivers HPV E7 antigen fused to non-hemolytic listeriolysin O protein 1, 2

ISA101

• Synthetic long-peptide HPV-16 vaccine
• Currently being evaluated in combination with nivolumab (anti-PD-1) in phase II trial (NCT02426892)
• Shows potential for enhancing immune response when combined with checkpoint inhibitors 1

GX-188E DNA Vaccine

• DNA-based vaccine targeting HPV antigens
• Being combined with pembrolizumab in the phase II KEYNOTE-567 trial (NCT03444376)
• Represents a promising approach to overcome immune suppression in the tumor microenvironment 1

BVAC-C Vaccine

• B cell-based and monocyte-based vaccine targeting E6 and E7 HPV oncoproteins
• Being investigated in phase II study (NCT02866006) as:
  • Monotherapy
  • In combination with topotecan chemotherapy 1

Novel Combination Approaches

Vaccines with Checkpoint Inhibitors

• Combining HPV-targeting vaccines with immune checkpoint inhibitors shows enhanced efficacy:
  • ISA101 with nivolumab (NCT02426892)
  • GX-188E with pembrolizumab (KEYNOTE-567)
• These combinations may help overcome resistance to single-agent immunotherapies 1, 3

Bintrafusp Alfa (M7824) Combinations

• Bifunctional fusion protein containing:
  • TGF-β "trap" (extracellular domain of TGF-βRII receptor)
  • Anti-PD-L1 antibody
• Being combined with HPV-targeting vaccines in ongoing trials:
  • NCT04287868
  • NCT04708470
• Addresses both TGF-β signaling (upregulated in HPV infection) and PD-L1 immune checkpoint 1

Vaccines with Radiation Therapy

• Radiation modulates the immune system through:
  • Inducing type I IFN expression
  • Promoting antigen release to activate adaptive immune response
• Several trials investigating chemoradiation therapy with immune checkpoint inhibitors
• Note: The phase III CALLA trial (CRT plus durvalumab vs. CRT alone) did not reach its primary PFS endpoint 1

Adoptive Cell Therapies Incorporating Vaccination Concepts

LN-145 TIL Therapy

• Tumor-infiltrating lymphocyte therapy for advanced cervical cancer
• Phase II trial (NCT03108495) showed:
  • 44% objective response rate
  • 89% disease control rate at 3.5 months follow-up
• Received FDA breakthrough therapy designation in 2019 1

Other Cellular Approaches

• T cell receptor (TCR)-engineered cell therapy
• Natural killer (NK) cell therapies
• Chimeric antigen receptor (CAR) T cell therapy
• These approaches may be enhanced by dendritic cell vaccines or viral gene delivery of E6/E7 1

Clinical Implications and Recommendations

• For patients with cervical cancer, clinical trial enrollment should be prioritized whenever feasible 1
• Non-FDA-approved immunotherapy combination strategies should only be considered in clinical trials 1
• Therapeutic cancer vaccines may benefit patients who are resistant to standard-of-care immunotherapies 4
• Vaccines targeting "stemness," epithelial-to-mesenchymal transition, and drug-resistant populations represent future directions 5

Important Considerations

• Therapeutic cancer vaccines differ from preventive vaccines by focusing on clearing active disease rather than prevention 6
• Cancer antigens tend to induce weaker immune responses than "foreign" antigens from infectious agents, requiring potent adjuvants 6
• The tumor microenvironment plays a critical role in determining vaccine efficacy 5
• Patient selection is crucial for maximizing clinical benefit from cancer vaccines 5

The development of effective therapeutic cancer vaccines represents a significant opportunity to expand treatment options for patients with various cancers, particularly those who have failed or are ineligible for standard therapies.