The MAB Who Would Be King Rituximab, Cetuximab, Bevacizumab, Alemtuzumab, Trastuzumab

3.2 – “The MAB wh who o would be king king”: ”: Rituximab, cetux cetuximab, imab, bevac bevacizumab, izumab, alemtuzuma alemtuzumab, b, trastuzumab • Antibodies used in treatment of B-cell lines, created by a single cell line, hence monoclonal Ab. -mab = monoclonal Ab; -ximab = chimeric Ab – human derived + mouse derived variable region; -zumab = humanized Ab. • Rituximab (coronation ritual) o Chimeric Ab targeting CD20 (chimera sigil; XX straps). Results in in depleting B-cells and increases cellular killing via targeting for killing. o Indications ▪ CD20 ⊕ hon-Hodgkin lymphomas ▪ CLL (abnormal proliferation of abnormal B-cells & T-cells) (chronically worn tapestry with B-cell archers & T-cell knights) ▪ Disease modifying anti-rheumatic drug (DMARDs) (joint lantern with inflammatory candle). Usually in combination with MTX for treatment-resistant RA. ▪ Immunosuppressive therapy, including for granulomatosis with polyangiitis, microscopic polyangiitis (torn Ab lantern) o Adverse effects ▪ Immunosuppression (bishop’s cane). Not as much as one might expect, as Ig levels generally stay fairly normal. May see immunosuppression d/t neutropenia ▪ Hep B reactivation ▪ Rarely associated with progressive multifocal leukoencephalopathy, from the JC virus (laurel leaves) ▪ Infusion reaction common in 50% of patient. Presents headache, fever, rash, puritis, dyspnea, hypotension (swollen pink cherub with ivy). Thought to be d/t Ag-Ab interaction → activation of immune cells • Managed with antihistamines, acetaminophen, NSAIDS ▪ Serum sickness – type III HS reaction, resulting from tissue deposition of circulating immune complexes, causing fever, rash, arthralgia, proteinuria, LAD within 7-10 days (Delayed onset poisoning) • Occurs d/t targeting of non-human Ab components • Cetuximab (elephant tusks) o Binds EGFR (giraffe). EGFR acts via a tyrosine kinase. o Adverse effects ▪ Infusion reaction common in 50% of patients e.g. headache, fever, rash, puritis, dyspnea, hypotension (swollen pink cherub with ivy). Thought to be d/t Ag-Ab interaction → activation of immune cells • Managed with antihistamines, acetaminophen, NSAIDS ▪ Serum sickness – type III HS reaction, resulting from tissue deposition of circulating immune complexes, causing fever, rash, arthralgia, proteinuria, LAD within 7-10 days (Delayed onset poisoning) • Less common than in rituximab • Bevacizumab (beverage lady) o VEGF inhibitor by binding directly to VEGF (chopped vegetables). Anti-angiogenic (chopped vascular vegetables) o Useful for treating certain metastatic cancers (Cracked crabs) o Used for wet macular degeneration, characterized by retinal hypoxia → subretinal VEGF production → angiogenesis (pillow with macular wet spot) o Adverse effects ▪ Bleeding, sometimes serious and even fatal (bloody aprons) ▪ ↑thromboembolic events (clot cubes) ▪ GI perforation (perforated sack of vegetables). Most commonly in metastatic CRC, epithelial ovarian CA. • Alemtuzumab (Alms) o IgG monoclonal Ab that binds CD52 found on normal & malignant cells of lymphoid lineage (natural killer cells, B & T cells). Initiates direct cytotoxicity by recruitment of complement. (Alms-seeker is begging from archer and knight; 52 design etched on knight’s scabbard) o Used in treatment of CLL (chronically worn tapestry with B-cell archers & T-cell knights) o Adverse events ▪ Marrow suppression, increased risk of AI disorders, infection risk • Trastuzumab (tapestry weaver) o Monoclonal antibody against HER2/neu ⊕, a Y-kinase (tire swing with her 2 babies). Inhibits MAPK & PI3K/AKT signaling pathways, & facilitates antibody mediated destruction tumor cells. ▪ HER2 ⊕ seen in 20% of breast CA (crab bra), as well as adenocarcinomas of the ovary, lungs, stomach, salivary glands. o Adverse effects ▪ Cardiotoxicity (unraveling heart tapestry). Presents most often as ↓LVEF, less commonly as HF. Generally resolves with cessation of treatment.