TUMOR IMMUNOLOGY
formation of cancer/tumorigenesis
Imbalance between cellular proliferation
and cellular death/apoptosis
caused by progressive growth
metastatic /benign
type of cell death
necrosis
apoptosis
Factors contributing to tumorigenesis
activating invasion and metastasis
inducing angiogenesis
avoiding immune destruction
enabling replicative immortality
evading growth suppresors
tumor antigen
tumor specific antigen (TSA)
tumor associated antigen (TAA)
categories of tumor antigen
viral gene product/cellular transformation
oncofetal antigen/cancer germline
oncogene
mutant cellular gene product/cellular transformation
goal of tumor immunology
elucidate immunologic relationship between host and tumor
utilize the immune reponse to tumor for the purpose of diagnosis,prophylaxis,and therapy
Immune responses against tumor cells
The immune system recognizes and reacts
against cancers
immune response against tumors is often
controlled by regulation or tolerance
Evasion of host immune system is one of the
hallmarks of cancer
Immune surveillance: concept of immunologic resistance
against the development of cancer
Elimination phase: Immune system recognizes and
destroys potential tumor cells
Equilibrium phase: elimination phase is not
successful;
Escape phase: tumor cells that have acquired the ability to evade immune system and grow
unimpeded become clinically detectable
Cell-mediated responses to tumor cells
Destruction of tumor cells by T lymphocytes
Antibody-Dependent Cell-Mediated Cytotoxicity
Destruction of Tumor by NK Cells
Effector mechanisms in tumor immunity
Antibodies and B cells
T cells
NK cell
macrophages and neutrophils
cytokines
complement mediated lysis,
opsonization)
cytolysis, apoptosis
cytolysis, apoptosis
Cytolysis, phagocytosis
Apoptosis, recruitment of
inflammatory cells
Tumor markers
is biological substance synthesized and
released by
tumor
host in reponse to tumor tissue
used to:
. 1.Establish the diagnosis
- Detect the presence of a tumor
- Monitor the progress of disease and response to treatment
- Detect the recurrence
- Determine the risk i.e genetically predisposed tumor
Tumor
Immunotherapy
Tumor-specific monoclonal
antibodies
Xenogeneic chimeric antibodies
Antibody–drug conjugates
Immunostimulatory monoclonal
antibodie
Identification of Neoantigen
Neoantigen: a mutated antigen that
forms on cancer cells within mutation that occur in tumor DNA
Radiolabeled tumor
specific antibodies
Injection of radiolabeled tumor-specific
antibodies
allows the detection of small
metastases as well as the primary tumor mass
Detection of Myeloma Proteins Produced by
Plasma Cell Tumors
Detection of α-Fetoprotein
Detection of Carcinoembryonic Antigen
Detection of Prostate-Specific Antigen
Detection of Cancer Antigen-125
Immunization against oncogenic virus
type of vaccine
Viral vectors (ie vaccinia) to vaccinate the host -
Naked DNA plasmid constructs (DNA vaccines)
Issues in development of vaccines against tumor
These antigens should be able to cross react immunologically with any prepared
vaccines
specific antigen