Chapter 8 anticancer - immuno-oncology agents

Question 1

ipilimumab (yervoy)

checkpoint inhibitor

Answer 1

• CTLA-4 inhibitors — augments T cell activation and proliferation
• monoclonal antibody that blocks cytoxic T lymphocyte antigen 4, which would usually block T cell activation (plus tumor infiltrating lympchotes that recognize and kill cancer cells)

indication
* melanoma

effects
* immune mediated inflammation of various tissues and organs

Question 2

pembrolizumab (keytruda)
nivolumab (opdivo)
cemiplimab (libtayo)

checkpoint inhibitor

Answer 2

PD1 inhibitors

• stops death ligand 1 (PD-L1) from binding to PD-1 (receptor) on activated t cells (usually when they bind; the t cell becomes docile or die)
• also augments T-cell activation + proliferation

effect
* immune mediated inflammation of tissue + organs

Question 3

avelumab (bavencio)
atezolizumab (tecentriq)
durvalumab (imfinzi)

checkpoint inhibitor

Answer 3

monoclonal antibody binds to PD-L1 rather than PD-1 receptor

Question 4

brentuximab vedotin (adcetris)

antibody drug conjugate

Answer 4

• monoclonal antibody
• delivers monomethyl auristatin E (MMAE) to cancer cells that expresse CD30 (hodgkins lymphoma)
• MMAE —- enters cell and disrupts microtubules => killing cell

Question 5

ado-trastusumab emtansine (kadcycla)

antibody drug conjugate

Answer 5

• monoclonal antibody
• delivers emtansine to cancer cells that express HER2 (breast cancer)
• beneficial to those w/ HER2-positive breast cancer patients (espeically those who fail Herceptin)

Question 6

moxetumomab pasudotox-tdfk (lumoxiti)

antibody drug conjugate

Answer 6

• Fc fragment of anti-CD22 monoclonal antibody taht delivers the pseudomonas exotoxin A to cells that express CD22 (hairy cell leukemia cells)

effects:
* capillary leak syndrome (acute and severe recurrent attacks associated with a rapid fall in blood pressure as a result of fluid leaks from smaller vessels called capillaries. Attacks often last several days and require emergency care)
* hemolytic uremic syndrome ( Infection with HUS causes destruction of red blood cells, which can then cause kidney failure. )
* renal toxicity
* electrolyte imbalance
* CD22 is expressed on b - cells there fore b cell population dwindles as side effect

Question 7

gemtuzumab ozogamicin (mylotarg)

antibody drug conjugate

Answer 7

• monoclonal antibody
• delivers ctyotoxic agent calicheamicin to cells that express CD33, such as acute myelogenous lekemia (AML)

Question 8

inotuzumab ozogamicin (besponsa)

antibody drug conjugate

Answer 8

monoclonal antibody
* delivers cytotoxic agent calcheamicin to cells that express C22, such as b-cell precursor acute lymphoblastic lekemia (pre-B-ALL)

effect
* hepatotoxicity inclduign veno-occlusive disease (happens when the small blood vessels that lead into the liver and are inside the liver become blocked. VOD is caused by high doses of chemotherapy and radiation therapy given before an. allogeneic.)

Question 9

rifuximab (rituxan)
oftaumumab (arzerra)
ibritumomab (zevalin)
obinutuzumab (gazyva)
tositumomab (bexxar)

monoclonal antibodies cont

Answer 9

• monoclonal AB that block CD20
• expressed in B-cell leukemias and lymphomas (complement dependent cytotoxicity?)
• present on normal B cells (cause transient immunodeficiency but are later replaced)

Question 10

traztuzimab (herceptin)
pertuzumab (perjeta)

monoclonal antibodies cont

Answer 10

recombinant humanized MAB that binds to extracellular portion human epidermal gorwth factor 2 (HER2) protein

indication
* breast cancer that overexpress HER2

Question 11

alemtuzumab (campath)

monoclonal antibodies cont

Answer 11

• recombinant humanized MAB that binds to CD52, an antigen on B and T lymphocyte

indication
* approved for b-cell chronic lymphocytic leukemia

Question 12

mogamulizumab-kpkc (poteligeo)

monoclonal antibodies cont

Answer 12

recombinant humanized MAB that bind to CCR4 (Receptor for chemokines — CCL2, 4, 5, 17, 22)
* these chemokines normally regulate trafficking of WBCs

indication
* cutaneous T-cell lymphoma

Question 13

daratumumab (darzalex)

monoclonal antibodies cont

Answer 13

• recombinant humanized MAB that binds to CD38
• cell surface protein highly expressed in multiple myeloma (Multiple myeloma is a cancer of plasma cells. Normal plasma cells are found in the bone marrow and are an important part of the immune system.) and expressed on some normal WBCs

Question 14

dintuximab (unituxin)

monoclonal antibodies cont

Answer 14

• chimeric human-mouse anti-glycolipid disialoganglioside (anti-GD2) antibody used to tx **neuroblastoma ** (cancers that start in early nerve cells (called neuroblasts) of the sympathetic nervous system, so they can be found anywhere along this system. Most neuroblastomas begin in the abdomen, either in an adrenal gland or in sympathetic nerve ganglia)

Question 15

thalidomide (thalidomid)
lenalidomide (revlimid)
pomalidomide (pomalyst)

other immuno-oncology agents

Answer 15

• multiple meyloma patients
• thalidomide binds to and blocks protein cereblon, which controls immunomodulation — likely responsible for anti-cancer actiivty
• lenalidomide – anemia, multiple myeloma, myelodysplastic syndrome (group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. The different types of myelodysplastic syndromes are diagnosed based on certain changes in the blood cells and bone marrow) in pateints w/ 5q chromosome deletion
• pomalidomide — multiple myeloma

Question 16

interferon

Answer 16

• enhance activity of cytotoxic T, NK cells, and macrophages
• inhibit proliferation of tumor cells

indication
* hairy cell leukemia (type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell))
* AID related kaposi’s sarcoma ====>
cancer that develops from the cells that line lymph or blood vessels. It usually appears as tumors on the skin or on mucosal surfaces such as inside the mouth, but these tumors can also develop in other parts of the body, such as in the lymph nodes (bean-sized collections of immune cells throughout the body), the lungs, or digestive tract.

The abnormal cells of KS form purple, red, or brown blotches or tumors on the skin. These affected areas are called lesions. The skin lesions of KS most often show on the legs or face. They may look bad, but they usually cause no symptoms. Some lesions on the legs or in the groin area may cause the legs and feet to swell painfully.

KS can cause serious problems or even become life threatening when the lesions are in the lungs, liver, or digestive tract. KS in the digestive tract, for example, can cause bleeding, while tumors in the lungs may cause trouble breathing.

Question 17

levamisole

Answer 17

• complex action on immune system
• enhances the depressed immune fx (antibody production)
• t cell, macrophage, and monocyte activation
• used in conjunction with flurouracil for advanced colon cancer following resection