Monoclonal Aby therapies

Question 1

Compare and contrast the effects that DARA and CAMELLIA have on serological testing

Answer 1

DARA: interferes w/ screen, ID, XM on IAT. Doesn’t interfere w/ ABO/Rh grouping @ RT
CAMELLIA: interferes w/ IAT & ABO/RH grouping

Question 2

Why are (0.2M) DTT treated reagent cells (AABB) used for DARA interferances

Answer 2

• bc Disrupts the S-S bond in the extracell. of CD38 = prevent DARA binding
  *But since DTT denatures other Ag like Kell (& dombrock) = difficult to ID a-K Aby

Question 3

What’s the pretransfusion procedures for pts on DARA

Answer 3

*Communication w/ Dr/Pt about medication/therapy
1. Baseline group & screen (w/ DTT treated reagent cells)
2. Extended phenotype or *Genotype IF recent transfusion &/or pos DAT: give match RBC

Question 4

What RBC units are selected for pts on DARA & what’s the XM steps if have:
a) NEG Aby screen
b) POS Aby screen
*used DTT treated reagent cells

Answer 4

a) IS or electronic XM using ABO/Rh AND Kell campatible units (Pheno/Geno-type match RBC where possible)
b) Aby ID using DTT-treated panel cells & select Ag neg cells & pheno/genotype-match RBC where possible. XM by IAT using DTT-treated donor cells

Question 5

Compare these methods for overcoming DARA interferances
a) AABB
b) Osaka
c) Daudi cells

Answer 5

a) 0.2M DTT treated cells
b) 0.01M (/10mM) DTT treated cells
c) fragments of daudi cell membrane - Hi CD38 expression: adsorb DARA from pt plasma & allowing detection of anti-K Aby

Question 6

What is DARA therapy. aka Daratumumab / Darxalex

Answer 6

• treat relapse or refractory MM (bc CD38 overexpressed in MM cells)
• Anti-CD38 (IgGI subtype) = binds to CD38 = destroys cell/s when bound (RBC also express CD38)

Question 7

What is CAMELLIA therapy. aka Hu5F9-G4

Answer 7

• treat haematologic malignancies & solid tumours
• Anti-CD47, *IgG4 subtype
• CD47 expressed on all cell types
  -NOTE: expression of CD47 on Ca cell avoids phagocytosis bc disguises as normal cell

Question 8

What methods are there in overcoming CAMELLIA interferances?

Answer 8

Gamma-clone IAT reagent (anti-IgG) = IAT not affected

Question 9

Whats the relationship b/w RHCE & CD47

Answer 9

• CD47 forms complex w/ D Ag
• proportional to each other
  e.g. more RHCE (e.g. in D pos) = More CD47

Question 10

What’s the pretransfusion procedures for pts on CAMELLIA

Answer 10

1. Serological tests: Group & screen (same as DARA)
2. Adsorb pt plasma w/ papain (Hi Sn) treated R1R1, R2R2 & rr cells: remove CAMELLIA leaving allo Aby
3. use gamma-clone anti-IgG on IAT test.
   * select pheno/genotype-match RBC