Immuno-Oncology for the Oncology Nurse *Funding for development of this activity was provided by an independent educational grant from Bristol-Myers Squibb.
Introduction to Immunotherapy
The Immune Response: Terminology Immunity: • The body’s ability to resist disease • Ability of the body to respond to foreign substances (microbes and noninfectious molecules) Immune system: • Network (cells, proteins, tissues, organs and molecules) that works together to defend the body against attacks by foreign invaders. Immune response: • Coordinated reaction of cells and molecules of the immune system (G. P. Dunn & Okada, 2015)
The Immune System: Self vs Non-Self • The key to a functional immune system is the ability to distinguish between self and non-self. - Cells carry self marker molecules (SELF). - Cells carry markers that are not recognized as self (FOREIGN) → immune response • Antigens trigger the immune response. - Microbe (e.g., virus) - Part of a microbe Tumor antigens are recognized as foreign by the immune system and initiate an immune response.
Innate Immunity Adaptive Immunity Antibodies T Cell B Cell Macrophages Dendritic T Cell Eosinophil Natural Killer Cell Neutrophil CD4+ T Cell CD8+ T Cell Natural Killer Cell Basophil
Non-Specific: Innate Lack Enhances adaptive Inflammation is one Limited immune response Speed immunologic Nonspecific of the first responses duration through presentation of of innate immunity. memory antigens Antigen-Specific: Adaptive Two types of adaptive response: • Humoral immunity: antibodies Develops slowly and provides a more specialized • Cell mediated: T lymphocytes defense against infections
Natural Killer Cells Cytokines B Cells CD8+ Killer T Cells Antibodies Identify and eliminate Help immune cells Release antibodies to Seek out and destroy Bind to antigens cells that fail to communicate and defend against threats. cancer cells. and mark cells produce self-MHC coordinate the right for attack and class molecules. response. destruction. Macrophages Regulatory T Cells Dendritic Cells CD4+ Helper T Cells Engulf and destroy Provide checks and Digest foreign cells Send “signals” to other harmful cells and balances to ensure and present their immune cells (B cells, present antigens to the immune system proteins to immune CD8+ T cells) to make other immune cells. doesn’t overreact. cells for destruction. them more efficient. Images used with permission from the Cancer Research Institute.
Natural Killer Cells Cytokines B Cells CD8+ Killer T Cells Antibodies Identify and eliminate Help immune cells Release antibodies to Seek out and destroy Bind to antigens cells that fail to communicate and defend against threats. cancer cells. and mark cells produce self-MHC coordinate the right for attack and class molecules. response. destruction. Macrophages Regulatory T Cells Dendritic Cells CD4+ Helper T Cells Engulf and destroy Provide checks and Digest foreign cells Send “signals” to other harmful cells and balances to ensure and present their immune cells (B cells, present antigens to the immune system proteins to immune CD8+ T cells) to make other immune cells. doesn’t overreact. cells for destruction. them more efficient. Images used with permission from the Cancer Research Institute.
Natural Killer Cells Cytokines B Cells CD8+ Killer T Cells Antibodies Identify and eliminate Help immune cells Release antibodies to Seek out and destroy Bind to antigens cells that fail to communicate and defend against threats. cancer cells. and mark cells produce self-MHC coordinate the right for attack and class molecules. response. destruction. Macrophages Regulatory T Cells Dendritic Cells CD4+ Helper T Cells Engulf and destroy Provide checks and Digest foreign cells Send “signals” to other harmful cells and balances to ensure and present their immune cells (B cells, present antigens to the immune system proteins to immune CD8+ T cells) to make other immune cells. doesn’t overreact. cells for destruction. them more efficient. Images used with permission from the Cancer Research Institute.
Natural Killer Cells Cytokines B Cells CD8+ Killer T Cells Antibodies Identify and eliminate Help immune cells Release antibodies to Seek out and destroy Bind to antigens cells that fail to communicate and defend against threats. cancer cells. and mark cells produce self-MHC coordinate the right for attack and class molecules. response. destruction. Macrophages Regulatory T Cells Dendritic Cells CD4+ Helper T Cells Engulf and destroy Provide checks and Digest foreign cells Send “signals” to other harmful cells and balances to ensure and present their immune cells (B cells, present antigens to the immune system proteins to immune CD8+ T cells) to make other immune cells. doesn’t overreact. cells for destruction. them more efficient. Images used with permission from the Cancer Research Institute.
Natural Killer Cells Cytokines B Cells CD8+ Killer T Cells Antibodies Identify and eliminate Help immune cells Release antibodies to Seek out and destroy Bind to antigens cells that fail to communicate and defend against threats. cancer cells. and mark cells produce self-MHC coordinate the right for attack and class molecules. response. destruction. Macrophages Regulatory T Cells Dendritic Cells CD4+ Helper T Cells Engulf and destroy Provide checks and Digest foreign cells Send “signals” to other harmful cells and balances to ensure and present their immune cells (B cells, present antigens to the immune system proteins to immune CD8+ T cells) to make other immune cells. doesn’t overreact. cells for destruction. them more efficient. Images used with permission from the Cancer Research Institute.
Natural Killer Cells Cytokines B Cells CD8+ Killer T Cells Antibodies Identify and eliminate Help immune cells Release antibodies to Seek out and destroy Bind to antigens cells that fail to communicate and defend against threats. cancer cells. and mark cells produce self-MHC coordinate the right for attack and class molecules. response. destruction. Macrophages Regulatory T Cells Dendritic Cells CD4+ Helper T Cells Engulf and destroy Provide checks and Digest foreign cells Send “signals” to other harmful cells and balances to ensure and present their immune cells (B cells, present antigens to the immune system proteins to immune CD8+ T cells) to make other immune cells. doesn’t overreact. cells for destruction. them more efficient. Images used with permission from the Cancer Research Institute.
Immunotherapy Principles
Cancer cells are different than healthy cells. Malignant tumor
Immunoediting: Cancer and Immunity Cancer Progression
The Cancer Immunity Cycle Release of cancer cell antigens (1) Cancer Killing of antigen cancer cells presentation (7) (2) Recognition Priming and of cancer by T activating cells (3) (6) Infiltration of Trafficking of T cells into T cells to tumor tumor (5) (4) (Chen & Mellman, 2013)
Types of Immunotherapy
Types of Immunotherapy Monoclonal Adoptive Cell Checkpoint Vaccines/Oncolytic Cytokines Antibodies Transfer Inhibitors Viruses • Living immune cells • Immunomodulatory • Harness memory • Tumor-targeting • Interferons and mAbs modified to trigger mAbs cell function of the interleukins an immune • De-suppress the immune system to • Boost immune • Set in motion a response create sustained stimulation immune response general immune immunity. pathways. (“release the response, activating brakes”). a wide range of immune cells.
Monoclonal Antibody (mAb): Basic Structure
Monoclonal Antibodies: Function Block growth Deliver other Flag cancer cells signals and anticancer agents to for destruction. receptors. the site of the tumor.
Some Common Monoclonal Antibody Targets Target Mechanism Example Agents Applications in Cancer CD20 Transmembrane protein that serves as a calcium channel rituximab, NHL, CLL implicated in activation, proliferation, and differentiation of B cells; obinutuzumab, present in the majority of B-cell NHLs and CLL; targeting CD20 ofatumumab leads to rapid cell lysis CD22 Role in establishing a baseline level of B-cell inhibition; helps inotuzumab, ALL maintain homeostasis in humoral immunity; expressed in majority ozogamicin of B-cell ALL HER2 Transmembrane receptor tyrosine kinase; overexpressed in some pertuzumab, Breast breast cancers trastuzumab EGFR Regulates epithelial tissue development; targeting can inhibit cetuximab Colorectal, signaling pathways leading to cell lysis and induce an immune lung response against cells with binding receptors
Tumor cell Cancer Vector- Vaccines in Cancer Antigen based Vaccines Dendritic
Oncolytic Viruses: Triggering the Immune Response Virus infects Normal cell Virus infects but cannot other tumor Unharmed replicate cells. Released Oncolytic virus antigens promote anti- tumor immune response. Tumor cell lysis causing Virus infects and Tumor cell release of viral particles replicates. and tumor antigens (Chen & Mellman, 2013)
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