Immune Therapy-Oncology Flashcards
REVIEW: What drug is able to target HER2?
- Tucatinib
REVIEW: What drugs targets a kinases that is produced by the formation of the Philadelphia chromosome?
- Imatinib
REVIEW: What drugs is not a covalent kinase inhibitor?
- Gefitinib
What was the first attempt to use immunotherapy?
- Coley’s Toxin: Basically bacteria that was injected into the tumor to start immune response
Within the cells of the immune system, which one are the most important?
- T & B Cells [Adaptive Immunity]
What are B Cells?
- Antibody producing cells
- B Cell is triggered by antigen and engulfs it, that makes antigen fragments to help attract the matching T Cell with makes the antibodies
What are some of the common nomenclatures for monoclonal antibodies?
Stem:
- mab
Substem:
- Mouse: -o-
- Chirmeric: -xi-
- Humanized: -zu-
- Fully Human: -u-
What does it mean when antibodies are two tiered?
- They are able to affect several cancer events
- Binding several antibodies to the cancer surface could lead to CDC, ADCC, and elimination of the Tumor cell
What is CDC and ADCC in terms of cancer and oncolgy?
- CDC: Complement-dependent cytotoxicity
- ADCC: antibody-dependent cellular cytotoxicity
What are the HER2 monoclonal antibodies that are used?
- Trastuzumab & Pertuzumab
What is the mechanism of action for trastuzumab?
- bind to the HER2 receptor and induce cytotoxicity [calling over NK cells]
- Will also decrease HER2 on the surface with degradation
What is the primary indication for Trastuzumab?
- Treatment of breast cancers with HER2 overexpression
What are some of the toxicites that are for Trastuzumab?
- Flu-like symptoms, Cardiomyopathy [increased with Adriamycin], NO myelosuppression
What is the important thing to know about Trastuzumab?
- Humanized monoclonal antibody for HER2
- Linked to Human IgG kappa?
What is the mechanism of action for Pertuzumab?
- Binds to HER2 to inhibit dimerization [dimerization is important for HER2 reponses]
What is the important thing to know about Pertuzumab?
- Humanized monoclonal antibody for HER2
What is the CLEOPATRA trial?
- It showed that Pertuzumab+Trastuzuamb was great
- NO differences in safety and increased survival
What was some ways that Fc engineering improved therapeutic antibodies?
- Margetuximab: increase in CD16A [NK Cells] & decrease in DC32B [B cells]
What are the EGFR monoclonal antibodies that are using cancer?
- Cetuximab & Panitumumab
What is the mechanism of action for Cetuximab?
- Binds to extra cellular EGFR that inhibits EGR & TGF leading to inhibition of Cell Growth and induce apoptosis
What is the primary indication for Cetuximab?
- Treatment for colorectal, head, and neck
What is important to know about Cetuximab?
- Chimeric antibody
What are some of the toxicities for Cetuximab?
- infusion reactions [1st dose]
- Rash
- Muscle weakness
- Fever
What is the mechanism of action for Panitumumab?
- Binds to the EGFR and inhibits the binding of EGF and TGF that leads to inhibition of cell growth and induce apoptosis
What are the side effects of Panitumumab?
- Skin rash
- Diarrhea
What is important to know about Panitumumab?
- Fully humanized monoclonal anitbody
What is the mechanism of action for Bevacizumab?
- Binds to VEGF that blocks the intercalation with endothelial receptor stoping cell proliferation
What is important to know for Bevacizumab?
- NOT good as single agent [combom with 5-FU]
- Humanized monoclonal antibody
Which one of the following antibodies targets HER2?
A] Neratinib
B] Cetuximab
C] Lapatinib
D] Pertuzumab
- Pertuzumab
What was the first immunotherapy?
- Coley Toxin
What type of antibody is fakeumab?
- Fully Human
What are the important B cell markers?
- CD20: affects the middle
- CD19: whole thing
- CD38: Early - Mid - End
How does CD20 work within B-Cell Receptors?
- Drives the proliferation [plays a role in lymphoma]
- Antibodies binding to CD20 can inhibit cell prliferation AND induce antibody-dependent cytotoxcity
How does CD38 work in B Cells?
- CD38 are highly expressed in plasma B cells that make antibodies [eliiminate multiple myeloma by ADCC and CDC
What is the mechanism of action for Trastuzumab-Emtansine [TDM1]?
- Binds to HER2 and enters the cell inhibiting microtubule assebly
What is important to know about Tratuzumab-Emtansine?
- Has BOTH cytoxic agent [Emtansine] & monoclonal antibody [Tratuzumab]
What are the toxicities of Trastuzumab-Emtansine?
- Adverse events of trastuzumab
- Thrombocytopenia
- Hepatotoxicity
What is the way that T-cells are made?
- Start in the bone marrow that moves to the thymus to mature
- T cell combines with MHC to become active and kill the cell
- T cells decrease making memory
What are some of the Bispecific T-cell Engagers [BiTE]?
- Blinatumomab, Mosunetuzumab,Teclistamab, Taquetamab
What is the mechanism of action for Blinatumomab?
- Binds to CD3 to bring an activated T-cell into range of CD19; which is highly expressed on B cell and Leukemia [lyase tumor]
- NOT chimeric
What is the mechanism of action for Mosunetuzumab?
- Targets CD3 and CD20 on non-Hodgkins
What is the mechanism of action for Teclistamab?
- Targets T cells and B cells on Myeloma cells
What is the mechanism of action for Taquetamab?
- Targets CD3 and Human GPRC5D on Myelona cells
What acts as “brakes” or “checkpoints” on the immue system?
- CTLA-4 and PD1
What drugs affect CTLA-4 and PD1?
- Ipilimumab, Pembrolizumab, Atezolizumab
What is the mechanism of action for Ipilimumab?
- Binds to CTLA-4 and reverse the CTL inhibition [CTL can destroy tumors]
- Treatment for metastatic melanoma
What are the side effects of Ipilimumab?
- GI issues
- Dermatitis
What is the mechanism of Pembrolizumab?
- Binds the PD-1 receptor and blocks its interaction with PD-L1/2 leading to tumor killing
What is important to know about pembrolizumab?
treatment?
- PD-1 = T cell
- PD-L1 = Tumor Cells
- Treatment for Metastatic melanoma [following Ipilimumab & BRAF] and NSCLC [PD-L1+]
What is the mechanism of action for Atezolizumab?
- Binds to PD-L1 and blocks the interaction with PD-1
