Cancer Treatment Modalities: Biotherapy (Immunotherapy and Targeted Therapy) Flashcards
Biotherapy =
Any form of treatment that uses the body’s natural abilities, or made from living organisms/lab to fight invading organisms, disease processes, or effects of treatment
Difference between biotherapy and chemotherapy =
Focus on body’s biologic role in tumor development or its response to a tumor or treatment (indirectly acts on immune system) vs. cytotoxic chemo affects all cells not just tumor cells
Targeted therapy =
Treatment that uses drugs or other substances to identify and attack specific cancer cells with less harm to normal cells
- some block action of certain enzymes, proteins, molecules involved in growth and spread of cancer cells
Immunotherapy =
Uses substances to stimulate or suppress immune system to help body fight cancer, infection, diseases
Growth signal inhibitors, Angiogenesis inhibitors, Apoptosis inducing drugs are all examples of?
Targeted therapy
Types of biotherapy (2)
Immunotherapy
Targeted therapy
Immunotherapy works by? (3)
1) Boost immune system
2) Enable immune system to
3) Recognize and fight tumor
Stop or slow cancer growth
Classes of immunotherapy (5)
1) Monoclonal antibodies
2) Vaccines
3) Cytokines
4) Adoptive cell therapy
5) Checkpoint inhibitors
Cytokines =
Hormone-like proteins with low molecular weight that are secreted by various cell types, which regulate intensity and duration of immune response and mediate cell to cell communication
Classes of Cytokines (3)
1) CSFs, HGFs, GCSFs
2) Interferons (IFN alpha 2a, beta 1a, beta 1b, gamma 1b)
3) Interleukins (ILs)
Mechanism of action of Interferons (INFs) =
Slows growth of cancer cells and encouraging normal cell behavior (naturally occurring substances in body)
Potential SE of Interferons (IFNs)
- Flu like sx
- Fatigue, Anorexia
- Neuropsychiatric sx
- Electrolyte disturbance
Example of an interleukin
IL-2
Mechanism of action of interleukins =
T cell growth factor
Stimulates growth of natural killer NK cells and cytotoxic T cells to enhance antibody response by binding to receptors on surface of T cells
Potential SE of Interleukins
- Capillary leak syndrome
- Hypotension
- Infusion reactions, rigors, chills, muscle pain, fever, SOB, skin rash/flushing
- Cardiac arrhythmia
- Diarrhea
Cancer Vaccines =
Treat existing* cancers or prevent development of cancer by boosting immune system
Cancer prevention (prophylactic) vaccines (2)
Hepatitis B vaccine -> prevents liver cancer
Human papillomavirus (HPVP -> prevents cervical cancer
Cancer treatment (therapeutic) vaccines (2)
Sipuleucel T -> hormone refractory prostate CA
Talimogene laherparepvec -> metastatic melanoma
Monoclonal antibodies =
Antibodies made in lab that target tumor specific antigens which are proteins that some tumors have
Can make many copies of that antibody hence monoclonal (mAbs)
What does it mean that mAbs are passive?
Do not result in any immunologic memory
3 most common monoclonal antibodies
Rituximab
Trastuzumab
Bevacizumab
How do mAbs work? (3)
1) Flag cancer cells for destruction
2) Block growth signals and receptors
3) Deliver other anticancer agents to site of tumor (when they are bound to other drugs or radiation particles, cancer cell engulfs and digests the mAb, attached chemo/radiation induces cellular death
Where are mAbs derived from before they get to the lab? Whose antibodies?
Human antibodies, animal antibodies, or a combination of the two
Types of mAbs derived from antibodies of
1) mouse
2) mouse and human
3) predominantly human
4) human only
1) Murine
2) Chimeric
3) Humanized
4) Human
Which antigens do these naked MOABS (those that can work alone) target?
1) Alemtuzumab (campath)
2) Trastuzumab (Herceptin)
3) Rituximab
4) Tositumomab
5) Obinutuzimab
6) Imatinib mesylate
1) CD52, CD20
2) HER2
3) CD20
4) CD20
5) CD20
6) Philadelphia chromosome
Mechanism of action of MOABS
Attaches to antigens expressed by specific cancer cells, acting as a marker for body’s immune system to destroy the cells
Antiangiogenic (anti-vascular endothelial growth factor) VEGF naked MOab agents =
Moabs that target the vascular endothelial growth factors that affects and may cause excessive tumor blood vessel growth (angiogenesis)
Examples of Antiangiogenic MOABS
Bevacizumab (Avastin) Pazopanib Sunitinib Sorafenib Axitinib Vandetanib
MoAb that treats CLL
Alemtuzumab (Campath) binds to CD52 antigen
MoAb that treats breast and stomach cancers that have antigen HER2
Trastuzumab (Herceptin)
Conjugated mAbs (2) =
tagged, labeled, loaded antibodies
mAbs combined with chemotherapy or radioactive particles
Radiolabeled antibodies
Chemolabeled antibodies
Ibritumomab tiuxetan (Zevalin) =
Radiolabeled mAb,
Targets CD20 antigen found on B lymphocytes
Tx for refractory or relapsed B Cell NHL
made of rituximab and radioactive substance (Yttrium-90)
Brentuximab Vedotin (Adcetris) =
Chemolabeled mAb
Targets CD30 antigen found on lymphocytes
Tx for refractory Hodgkin Lymphoma
Ado-Tastuzumab emtansine (Kadcyla, TDM-1) =
Chemolabeled mAb
Targets HER2 protein for Metastatic Breast CA
Attached to chemo drug DM1
Bispecific monoclonal antibodies =
Made up of 2 different mAbs -> can attach to 2 different proteins at the same time
Blinatumomab (Blincyto)
Bispecific mAb
Targets CD19 protein found on some leukemia and lymphoma cells and CD3 found on T cells
Cetuximab (Erbitux) =
Chimeric mouse and human antibody
Targets cell protein EGFR (epithelial growth factor receptor)
Adoptive T-Cell Transfer =
CAR-T cell
Collecting T cells which play a primary role in how immune system fights cancer from a patient and engineering them to recognize specific antigens on the surface of cancer cells -> then infusing them back into patient
Two major side effects of CAR-T cell therapy
Cytokine release syndrome
Neuro toxicities
Immune checkpoints =
Traffic lights that prevent over-activation of immune response (attack on healthy cells)
Key component of a healthy immune system
Examples of checkpoints on the surface of immune cells (3)
1) Programmed cell death protein (PD-1)
2) Programmed death ligand (PD-L1)
3) Cytotoxic T lymphocyte-associated protein 4 (CTLA-4)
Checkpoint inhibitors are a subset of?
mAbs
How do checkpoint inhibitors work on cancer?
release breaks on the immune system making it more likely to respond to tumor cells -> enhances T cell activity against tumor cells
Dose reductions are not possible with what immunotherapy?
Checkpoint inhibitors
irAEs =
Immune related adverse events
Most frequently cite iRAEs in clinical trials involving what 3 drugs?
Ipilimumab
Nivolumab
Pembrolizumab
Adverse effects of Ipilimumab
Fatigue
Diarrhea, colitis, enterocolitis
Hepatitis
Adverse effects of Nivolumab
Fatigue/musculoskeletal pain Pruritis Pneumonitis** Colitis Hepatitis* Endocrinopathies, hypophysitis (inflammation of pituitary gland), diabetes mellitus
Adverse effects of Pembrolizumab
Fatigue
Endocrinopathies, hypophysitis, diabetes mellitus
Pneumonitis
Hepatitis*
Because of the most common iRAEs what lab test should patients get?
Liver function tests
Risk for iRAEs may directly correlate with high level expression of what checkpoint inhibitor on tumor cells?
PD-L1
irAEs typically present when after initiating therapy?
6-12 weeks
irAES cited most frequently in dermatologic and gastrointestinal areas why?
Immune cells are most active in those areas
Targeted therapy =
Uses information about persons genes and proteins to target only a single or multiple abnormal protein on cancer cells without damaging normal cells
Targeted therapies work by (3)
1) Blocking angiogenesis
2) Blocking signals inside or outside the cell
3) Delivering toxic substances to the cell
Why is targeted therapy not always effective even though its suppose to work on your specific cancer?
Having the target does not mean the tumor will respond to the drug
Difference between targeted therapy and chemotherapy?
Chemotherapy is cytotoxic whereas targeted therapy is cytostatic (blocks tumor cell proliferation)
Types of Targeted therapy
Signal Transduction Inhibitors Tumor Specific Antigens Apoptosis Inducers Angiogenesis Inhibitors Small Molecule Agents Targeted Therapy
Signal Transduction Inhibitors =
Targeted therapy that blocks signal transduction that regulates cell growth, function, and apoptosis
Cell signals that come from outside the cell =
growth factors and growth factor receptors
Cell signals that come from inside the cell =
tyrosine kinase receptors
Process of cell signaling
Signal is transmitted by _____ to the cell’s control ____ (____) through a series of biochemical _____. Control center ____ these signals and produces an appropriate _____. Activation of ____ ___ triggers biochemical ____ of cell signaling events. In cancer these signals are _____ “on” and malignant cells are stimulated to _____ continuously without being prompted by outside signals.
proteins center (nucleus) reactions, reads response tyrosine kinases cascade stuck divide
Examples of signal transduction inhibitors used in treatment of cancer (5)
EGFR inhibitors HER2 inhibitors BCR-ABL (tyrosine kinase) inhibitors ALK (multikinase) inhibitors BRAF inhibitors
Examples of drugs that block the following signal transduction inhibitors
1) EGFR inhibitors
2) HER2 inhibitors
3) BCR-ABL (tyrosine kinase) inhibitors
4) ALK (multikinase) inhibitors
5) BRAF (multikinase) inhibitors
1) Cetuximab, Erlotinib
2) Trastuzumab, Pertuzumab
3) Imatinib, Dasatinib
4) Crizotinib, Certinib
5) Vemurafenib, Dabrafenib
Tumor specific antigen =
A protein or other molecule that is unique to cancer cells or is much more abundant in them
Tumor specific antigens are usually found in what part of the cell?
Plasma (outer) membrane
For a tumor antigen to be best suited for targeted therapy it should be
1) _____ to tumor cells
2) Located on the _____ of tumor cells
3) Present in ____ numbers
4) Involved in tumor cell _____
1) Specific
2) Surface
3) large
4) survival
Tumor specific antigens are very important in treating what types of cancers?
Leukemia, Lymphomas
CD20 =
Found on normal and malignant pre-B lymphocytes and mature B lymphocytes
Tx for certain types of B cell lymphomas and leukemia
What drug targets and destroys B cells that have CD20?
Rituximab
CD33 =
Found on myeloid (myeloid specific) cells but also some lymphoid
Tx for AML
CD52 =
A protein present on surface of mature lymphocytes but not on stem cells from which these lymphocytes were derived; also found on monocytes and dendritic cells associated with some types of lymphoma
Tx for some types of lymphoma
Drug that targets CD52, marking the CD52 lymphocytes for destruction =
Alemtuzumab
The CD Antigens (3)
CD20
CD52
CD33
Apoptosis Inducers =
Cause cancer cells to undergo apoptosis
Proteasome inhibitor =
An apoptosis inducer that stops proteasome from breaking down proteins that cause cell death -> cell death
What is a proteasome?
A complex of enzymes inside a cell that helps destroy proteins no longer needed by the cell
Bortezomib and Carfilzomib are examples of?
Apoptosis inducers
Angiogenesis Inhibitors =
Block tumor angiogenesis where tumors create their own blood supply needed for growth and metastasize
Two ways to inhibit tumor angiogenesis
1) Inhibit the action of what protein or receptor?
2) Target ____ on the surface of ____ cells or other proteins in downstream signaling pathways that stimulate a new blood ____ growth
1) Vascular endothelial growth factor (VEGF)
2) receptors, endothelial, vessel
Popular Angiogenesis Inhibitors (3)
Bevacizumab
Sorafenib and Sunitinib
Bevacizumab =
An Angiogenesis inhibitor that specifically recognizes and binds to VEGF
Tx for Metastatic Colorectal Ca
Bad for wound healing
Sorafenib and Sunitinib =
Angiogenesis inhibitors that bind to receptors on surface of endothelial cells or to other proteins in downstream signaling pathways, blocking their activities
Small molecule targeted therapies =
Developed for targets that are located inside* the cell (intracellular) because these agents are able to enter cells more easily -> disrupts function of cells, causing cell death
Examples of Small Molecule Agents (5)
1) Tyrosine Kinase Inhibitors (TKIs)
2) Tyrosine Kinase inhibiting MOABS
3) Kinase inhibitors
4) P13K inhibitors
5) Hedgehog pathway inhibitors
TKIs and Tyrosine Kinase Inhibiting MOABS
1) Which antigen is targeted?
2) Examples (7)
3) Mechanism of action:
1) Epidermal Growth Factor Receptor (EGFR)
2) END IN TINIB* for TKI
Cetuximab, Gefitinib, Erlotinib, Lapatinib, Panitumumab, Vandetanib, Zivaflibercept
3) TKIs bind to tyrosine kinase in EGFR -> inactivating or limiting its activity
How do monoclonal antibodies with TKI capabilities work?
They bind to extracellular component of EGFR to prevent actual substrates from binding to receptors, inhibiting EGFR activation
TKI drug route =
So those administering should be aware of
1) A____ to therapy
2) Interactions with:
Oral agents
1) Adherence
2) food/drug and drug/drug that influences when to take and what food/drink to avoid
Examples of TKIs
End in Tinib*
Erlotinib Sunitinib Ponatinib Imatinib Dasatinib Ibrutinib
TKIs and the cancers they treat
1) Erlotinib
2) Sunitinib
3) Ponatinib
4) Imatinib
5) Dasatinib
6) Ibrutinib
1) Advanced NSLCA and pancreatic CA
2) Advanced RCC, GIST (gastrointestingal stromal tumors)
3) CML
4) Philadelphia chromosome + CML
5) Philadelphia chromosome + CML
6) Mantle cell lymphoma, Waldenstroms macroglobulinemia, CML
Kinase Inhibitors
1) What is it?
2) Target what pathway?
3) Drug names end in?
4) Nursing considerations:
1) Type of Small Molecule Agent Targeted Therapy
2) RAF/RAS/MET pathway
3) nib
4) Oral agent -> be aware of drug/food interactions, when to take, foods to avoid
Examples of Kinase Inhibitors
Sorafenib
Dabrafenib
Trametinib
Vemurafenib
P13K Inhibitors
1) What is it?
2) Targets what pathway?
3) Drug names end in?
4) Nursing considerations:
1) Small molecule agent targeted therapy
2) P13K pathway
3) Lisib
4) Oral agent -> food/drug interactions, when to take, foods to avoid
Idelalisib =
Treats what? (2)
P13K inhibitor
1) Follicular B cell non-Hodgkin Lymphoma
2) Relapsed CLL
What is the Hedgehog pathway?
Aberrant signaling of this pathway leads to?
Plays a role in brain and spinal cord development and controls cell division and differentiation in adult stem cells
Different forms of cancer
Therefore, targeting this pathway may prevent/treat cancers
Hedgehog pathway inhibitors
1) What is it?
2) Drug names end in?
3) Nursing considerations:
1) Small molecule agent targeted therapy
2) Gib
3) oral agent -> food/drug interactions, when to take, what foods to avoid
Sonidegib and Vismodegib =
What conditions do they treat?
Hedgehog pathway inhibitors
Locally advanced basal cell carcinoma
Metastatic or recurrent local advanced basal cell carcinoma
Targeted therapy main side effects (5)
Infusion reaction/hypersensitivity Skin reactions Cardiovascular effects Bleeding and clotting abnormalities Impaired wound healing
Other SE
N/V, diarrhea/constipation, mucositis, cough, dyspnea, fatigue, HA, edema, organ toxicity, colitis, risk for infection
Hormone therapy =
Treatment that adds, blocks, removes hormones from body to help slow or stop growth of cancer cells
What are hormones? Where are they produced?
The body’s chemical messengers
Endocrine glands (thyroid, pancreas, ovaries, testes)
What type of cancers do hormone therapies usually treat?
Breast and Prostate
usually used with chemo/RT
Hormone therapy mechanisms of action (3)
1) Block hormone receptors
2) Blocks the body’s production of the hormone
3) Eliminates or changes shape of hormone receptors on cell surface
Examples of Hormone therapy drugs (4)
1) Antiestrogens (tamoxifen, fulvestrant)
2) Aromatase inhibitors (Anastrozole, exemestane)
3) Antiadrogens (Biculatamide, Flutamide)
4) Luteinizing hormone releasing hormone (LHRH) agonist (Goserelin, leuprolide)
