Personalized Cancer Vaccines

Revolutionizing the Future of Cancer Treatments

Personalized cancer vaccines represent a promising avenue in the quest for tailored and effective anticancer interventions. Like conventional vaccines, anti-cancer vaccines help your body identify cancer as a threat. However, unlike standard vaccines, personalized cancer vaccines leverage the patient’s unique genetic profile and tumor-specific antigens to elicit a targeted and robust immune response. This offers the potential for both enhanced therapeutic efficacy and reduced off-target effects. In some cases, they have been able to shrink tumors and extend survival in patients with advanced cancer.

There are many types of cancer vaccines, maiming differing in the material or method used to elicit an immune response. Tumor lysate vaccines use pulverized tumor tissue as a source material while target-specific vaccines pursue common cancer targets. Neoantigen vaccines are the most advanced type and require interrogation of the tumor by sequencing all DNA and RNA. These types of vaccines can also be produced with protein fragments called peptides or RNA as used in COVID vaccines.

Given the comprehensive research from numerous institutions on personalized cancer vaccines across various disease stages, we have highlighted recent articles from the last few years that evaluate the effectiveness and advancements of these vaccines in treating different forms of cancer.

How Can This Approach Help Patients?

Personalized cancer vaccines have diverse applications for active treatment, the prevention of cancer recurrence, and even the prevention of cancer development. They are a safe and effective tool that can support other treatments.

Unmet Need for A Challenging Cancer

Glioblastoma treatment is challenging and has a significant impact on patient outcomes and treatment efficacy due to obstacles such as tumor location, the impact of growth, and tumor heterogeneity1. Overall, the biggest problem is recurrence which can occur despite removing all visible tumor. Tumor lysate vaccines are among the first developed against cancer in the modern era and have been used for decades. This work culminated in one of the largest studies researchers found that integrating a dendritic cell vaccine called DCVax-L with standard of care resulted in a significant extension of survival for patients with both newly diagnosed and recurrent glioblastoma2. Lysate vaccines are met with the challenge of needing fresh tissue isolated during surgery. Therefore, researchers have sought other ways to trigger immune response.

Neoantigens are mutated proteins that are expressed on the surface of cancer cells. They are not present in normal cells, which makes them ideal targets for cancer vaccines. A neoantigen-based strategy was developed that elicited a potent, safe, and highly specific immune anti-tumor response in melanoma patients3. This neoantigen approach was adapted to glioblastoma patients, the vaccine was highlighted in stimulating robust immune responses. The results showed that the vaccination induced circulating neoantigen-specific T cell responses in patients who did not receive dexamethasone during vaccine priming. Additionally, the study provides compelling evidence of the migration of neoantigen-specific T cells from the peripheral blood into the intracranial glioblastoma tumor4.

Progress for the Most Aggressive Cancer

Pancreatic cancer is commonly acknowledged as an aggressive form of cancer characterized by late detection, rapid metastasis, invasive growth, and resistance to treatment5. These factors emphasize the urgent need for continual research and the development of more effective and targeted treatment strategies to improve patient outcomes and survival rates.

In a detailed case study involving a 62-year-old patient diagnosed with metastasized pancreatic ductal carcinoma, a multi-peptide vaccine was administered, targeting the specific mutations of the pancreatic tumor. With the use of TCR Sequencing, the T-cell responses observed possibly contributed to the patient’s clinical outcome, with the individual alive six years after the initial diagnosis6.

Several clinical trials are currently underway to evaluate the safety and efficacy of neoantigen vaccines for pancreatic cancer. A recent trial has published promising preliminary results evaluating the use of a personalized neoantigen vaccine in combination with atezolizumab and mFOLFIRINOX for individuals with pancreatic cancer whose tumors had been surgically removed.  After vaccination, half of the participants exhibited a substantial T-cell response to at least one vaccine neoantigen. Those who generated an immune response were less likely to have disease recurrence, possibly attributable to the presence of new, vaccine-induced, neoantigen-specific T cells capable of eliminating spreading tumor cells7. More research is needed to develop better ways to detect, diagnose, treat, and prevent pancreatic cancer.

Peptide Vaccines for Breast Cancer: A Hopeful New Approach

While significant strides have been made in recent years in the treatment of breast cancer, several challenges remain, including tumor stage at diagnosis, treatment resistance, tumor type variation, and tumor heterogeneity8,9.

A recent study explored the use of a personalized neoantigen peptide as an adjuvant treatment for patients with breast cancer. This approach entailed the use of a prophylactic peptide vaccination in four female breast cancer patients who had achieved remission following standard treatment. The patients underwent an initial assessment for somatic tumor mutations, followed by the administration of personalized neoantigen-derived peptide vaccines. Immune responses were elicited in all patients and the study demonstrated that the vaccination approach was feasible and safe10.

Many vaccines use different designs for neoantigens. The utilization of BioInformatic Tumor Address Peptides (BITAP) has shown the potential to improve the overall survival of patients diagnosed with HER2-positive metastatic breast cancer. The findings revealed that the use of BITAP resulted in stable disease and may induce tumor regressions in patients with HER2-positive subsets of breast cancer11.

Changing Medicine

Through their customizable nature, personalized cancer vaccines have the capacity to address the complexities and heterogeneity of different cancers. They hold the potential to help patients resistant to other standard-of-care immunotherapies, improving patient outcomes and survival rates across a wide range of malignances12.

They are used for a diverse range of cancer from bladder to prostate. A recently published case report demonstrates the potential of personalized neoantigen vaccines for the treatment of metastatic prostate cancer. The report involves a patient with metastatic castration sensitive prostate cancer who was treated with a personalized neoantigen vaccine as recurrence prophylaxis. The vaccine was well-tolerated and the patient had a significant clinical response, a decrease in tumor burden and improvement in symptoms13.

As personalized cancer vaccines continue to evolve and demonstrate their efficacy in clinical settings, they have the potential to significantly transform the landscape of cancer treatment, offering new hope for patients and contributing to the ongoing efforts to combat this challenging disease.

References

  1. Yuan, B., Wang, G., Tang, X., Tong, A. & Zhou, L. Immunotherapy of glioblastoma: Recent advances and future prospects. Hum. Vaccines Immunother. 18, 2055417.
  2. Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial | Neuro-oncology | JAMA Oncology | JAMA Network. https://jamanetwork.com/journals/jamaoncology/fullarticle/2798847.
  3. Personal neoantigen vaccine prompts strong anti-tumor response in patients, new study shows. https://www.dana-farber.org/newsroom/news-releases/2017/personal-neoantigen-vaccine-prompts-strong-anti-tumor-response-in-patients-new-study-shows.
  4. Keskin, D. B. et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 565, 234–239 (2019).
  5. Halbrook, C. J., Lyssiotis, C. A., Magliano, M. P. di & Maitra, A. Pancreatic cancer: Advances and challenges. Cell 186, 1729–1754 (2023).
  6. Sonntag, K. et al. Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report. J. Transl. Med. 16, 23 (2018).
  7. Rojas, L. A. et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature 618, 144–150 (2023).
  8. Nolan, E., Lindeman, G. J. & Visvader, J. E. Deciphering breast cancer: from biology to the clinic. Cell 186, 1708–1728 (2023).
  9. Aapro, M. et al. Current challenges and unmet needs in treating patients with human epidermal growth factor receptor 2-positive advanced breast cancer. Breast Off. J. Eur. Soc. Mastology 66, 145–156 (2022).
  10. Zelba, H. et al. Adjuvant Treatment for Breast Cancer Patients Using Individualized Neoantigen Peptide Vaccination—A Retrospective Observation. Vaccines 10, 1882 (2022).
  11. Schönharting, W. et al. Improved Survival of a HER2-Positive Metastatic Breast Cancer Patient Following a Personalized Peptide Immunization. Vaccines 11, 1023 (2023).
  12. Lin, M. J. et al. Cancer vaccines: the next immunotherapy frontier. Nat. Cancer 3, 911–926 (2022).
  13. Zelba, H. et al. Case Report: Targeting of individual somatic tumor mutations by multipeptide vaccination tailored for HLA class I and II presentation induces strong CD4 and CD8 T-cell responses in a patient with metastatic castration sensitive prostate cancer. Front. Immunol. 14, (2023).