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

  1. Detect the presence of a tumor
  1. Monitor the progress of disease and response to treatment
  1. Detect the recurrence
  1. 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