Cancer Immunotherapy : Stimulation of Host Antitumor Immune Responses by Vaccination With Tumor Antigens
المؤلف:
Abbas, A. K., Lichtman, A. H., & Pillai, S
المصدر:
Basic Immunology : Function and disorders of immune system
الجزء والصفحة:
6th ed , page 206-207
2025-05-28
468
One way of stimulating active immunity against tumors is to vaccinate patients with their own tumor cells or with antigens from these cells. Unlike standard antimicrobial vaccines, which are prophylactic in that they prevent infections, tumor vaccines are meant to be therapeutic, in that they stimulate immune responses to attack cancers that have already developed. An import ant reason for defining tumor antigens is to produce and use these antigens to vaccinate individuals against their own tumors. Most tumor vaccines tried to date have used antigens that are shared by the same type of cancers in different patients. These antigens are usually differentiation antigens that identify cells of a particular lineage, both normal and neoplastic. Vaccines incorporating such antigens have had little success, perhaps because the antigens are expressed at some level in normal cells and tend to induce tolerance that has to be overcome for induction of effective antitumor immunity.
More recently, there has been interest in developing personalized cancer vaccines tailored for each patient’s tumor. As we discussed earlier, the most common anti gens that induce immune responses in cancer patients are neoantigens generated by passenger mutations affecting random cellular proteins, and the mutations must be within peptides that can bind to the patient’s HLA molecules in order to recognized by T cells. A current focus of the tumor vaccination field is to use DNA sequencing technologies to determine all the mutations in the protein-coding DNA sequences (exosomes) of an individual’s cancer cell genome. HLA-binding pre diction algorithms are then applied to identify mutant peptides that are most likely to bind to the HLA alleles of the patient. After these peptides are defined, personalized tumor vaccines are created using several of the neoantigen peptides. This approach is promising, but it also has significant challenges. The vaccines have to be customized for each patient; effective CTLs have to be generated by the vaccination (which has been difficult to do so far with most vaccines, which work by stimulating production of antibodies); tumors may evolve under the selection pressure of the vaccine-induced immune response and lose MHC molecules or the target antigens; and because these are therapeutic vaccines given to tumor-bearing patients, they have to overcome the immune evasion mechanisms that tumors may have established in the patient.
Tumor-specific vaccines may be administered as a mixture of the antigen with adjuvants, just like antimicrobial vaccines. In another approach, a tumor patient’s dendritic cells are expanded in vitro from blood pre cursors, the dendritic cells are exposed to tumor cells or tumor antigens, and these tumor-antigen–pulsed dendritic cells are used as vaccines. The dendritic cells bearing tumor antigens will theoretically mimic the normal pathway of cross-presentation and will generate CTLs against the tumor cells. The success of checkpoint blockade therapies, described previously, has raised hopes that vaccination used in combination with therapies to block immune regulation will have added benefits.
Tumors caused by oncogenic viruses can be pre vented by vaccinating against these viruses. Two such vaccines that are proving to be remarkably effective are against hepatitis B virus (the cause of a form of liver cancer) and human papillomavirus (the cause of cervical cancer and some types of oropharyngeal cancer). These are prophylactic vaccines given to individuals before they are infected, and thus prevent infections by the tumor-causing viruses.
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