Tumor vaccine has been a hot topic of research in the field of tumor treatment. It works by introducing some component of the tumor into the patient’s body that stimulates the body’s immune system to kill and clear the tumor.
The tumor components introduced into the body can be proteins, peptides, genes, or cells. These components are specially treated as tumor antigens that are inactivated, attenuated, and not tumorigenic.
How do tumor vaccines work?
Vaccines primarily stimulate the body to produce the appropriate antibodies through exogenous antigens, stimulating an immune response that gives the body resistance to a particular disease.
Tumor cells also have specific “tags” that are easily recognized by the immune system, namely tumor antigens. Human epidermal growth factor receptor 2 (HER2) and mucin 1 (MUC1) are two of the most talked about antigens in breast cancer. Approximately 25% of breast cancer patients have tumor cells that HER2 overexpress, and almost all breast cancers have MUC1 overexpression.
The immune system distinguishes between breast cancer cells and normal cells by recognizing tumor antigens and subsequently mobilizing T lymphocytes or antibodies to attack the cancer cells. But this recognition is not very reliable, and the number of T cells and antibodies that can find HER2 or MUC1 is small.
So scientists want to amplify the immune function with a vaccine that is “labeled” (antigen-specific) to strengthen the immune system’s “fighting ability.
What are the breast cancer vaccines?
What are the vaccines for breast cancer?
There are two main types of breast cancer vaccines being studied: therapeutic vaccines and preventive vaccines.
Therapeutic vaccines are primarily used in breast cancer patients and include antigen-based vaccines (HER2 vaccine, p53 vaccine, etc.) and cell-based vaccines (dendritic cell vaccine and Lapuleucel-T etc.).
Prophylactic vaccines (e.g., E75 peptide vaccine) are used primarily in patients with otherwise treated breast cancer to prevent recurrence or to eradicate residual tumor antigens.
How do therapeutic vaccines work?
Antigen-based vaccines
HER2 vaccine: This vaccine induces T lymphocytes to function immunologically, producing antibodies to inhibit HER2 -positive cancer cell proliferation. A study of 22 metastatic breast cancer patients who were HER2 positive found that combined vaccination with HER2 vaccine on top of trastuzumab stimulated the immunity of the patient’s organism and maintained the immune function at a strong level. The patient tolerated well during the dosing period.
p53 vaccine: In the 1990s, researchers discovered that p53 antibodies could be detected in the serum of breast cancer patients, and perhaps p53 could also be used in the development of tumor vaccines.
The wtp53 (wild-type p53) vaccine has been tried for the treatment of tumors such as breast cancer. An exploratory phase II clinical study showed that in 26 patients with HLA-A2+ type advanced progressive breast cancer, the combination of recombinant human interleukin-2 and wtp53 vaccine led 8 to stable disease or mild remission, and the patients were induced to produce specific T lymphocytes. nbsp;The number of lymphocytes almost doubled.
In a phase I/II clinical study, p53 vaccine combined with an immune drug called indomethol treated 39 patients with metastatic solid tumors or invasive breast cancer. Of these 7 had detectable immune responses. The vaccination was followed by supplemental chemotherapy, with 9 benefiting and stable or improving tumors.
Cell-based vaccines
Dendritic cell vaccines: Dendritic cells (DCs) are the most powerful specialized antigen-presenting cells (APCs) in the body, and their role is to process cells with tumor antigen “tags” and deliver them to T lymphocytes, which are responsible for clearance and killing. DCs can carry some antigens into the body that can be used as therapeutic targets to induce an immune response.
Basic studies have shown that DCs carry MUC1 antigens and then form a vaccine that can successfully induce the production of corresponding T lymphocytes.
In an exploratory study, 54 breast cancer patients (including in situ and invasive cancers) were vaccinated with a DC vaccine carrying the HER2 antigen at the lesion and lymph nodes. The rates of complete pathological remission in patients with in situ and invasive breast cancer were 28.6% and 8.3%, respectively, and the rates of immune response in patients after vaccination were approximately 66.7% to 89.5%.
Lapuleucel-T: also known as APC8024, is a new immune cell vaccine. This vaccine is used in a very specific way, where mononuclear cells from the patient’s blood are isolated, added to a protein antigen called BA7072 and cultured in vitro and then infused back into the patient, which is equivalent to taking your own immune cells out of vitro and processing them to improve them, “targeting” HER2 positive tumor cells.
Early clinical studies found that breast cancer patients who received Lapuleucel-T had an immune response and a surge of T lymphocytes. 2 of 18 patients who received the vaccine maintained stable disease for more than 12 months.
How does the prophylactic vaccine work?
How does the preventive vaccine work?
Based on the different components of the HER2 protein, scientists have developed vaccines such as E75, AE37, and GP2. Prophylactic vaccines applied in conjunction with immune boosters can increase antigenicity. Related studies are currently underway and may have a role in preventing tumor recurrence.
In 186 patients with high-risk breast cancer who were partially vaccinated with a combination of E75 and granulocyte-macrophage colony-stimulating factor (GM-CSF) vaccine and followed for 20 months, the recurrence rate was found to be 5.6% and 14.2% in vaccinated versus unvaccinated patients, respectively. In addition, clinical studies of the E75 peptide vaccine in combination with trastuzumab for high-risk HER2 positive breast cancer are underway.
Outlook
Breast cancer vaccine research is still in the exploratory phase, and preliminary results are promising.
- Therapeutically, in situ and invasive breast cancers have achieved some pathologic complete remission after vaccination, and individual patients with HER2 positive advanced breast cancer have even been able to stabilize their disease for a long time.
- In terms of recurrence prevention, a small percentage of high-risk patients experienced a reduction in recurrence rates after vaccination.
Researchers are still looking for more active and specific tumor antigens in an effort to identify breast cancer populations that are better suited for tumor vaccination.