Monoclonal construct

Douglas H Thamm dthamm at
Sat Mar 8 10:33:15 EST 1997

I recently attended a seminar given by a post-doc in Paul Sondel's lab at 
the University of Wisconsin. He briefly mentioned a very interesting 
monoclonal construct directed against one of the melanoma-specific 
antigens. Basically, it consisted of the Vh and Vl chains, plus the 
linker region and cysteine residues, but attached to the Fc end was the 
zeta chain of CD3 (see the ASCII drawing below)

		Vh           Vh
		  \         /
		  Vl      Vl
		  |        |
		  |-S - S -|
		  |	   |
	          |-S - S -|
		  |	   |
		  |        |}-- TRANSMEMBRANE DOMAIN
		  |	   |
		 /          \
	      Zeta         Zeta

	However, no mention was given about how such a molecule would 
function. It seems that without being inserted into an approptiate T 
cell, there would be no signal to transduce. 
Hence, it would seem that the most practical use would be to engineer T 
cells to express this construct, expand them in culture and adoptively 
transfer the expanded cells. A heck of a lot of work. Could there be any 
potential application for the IV administration of such an antibody? Can 
anyone think of a less labor-intensive way to use such a construct? Any 


| A student asked his master, "Master, what is the Way?"           |
| The master slapped the student, and the student went away	   |
| 	enlightened.						   |
| Douglas H. Thamm, VMD         | Resident, Medical Oncology       |
| thammd at	| School of Veterinary Medicine    |
| dthamm at	| University of Wisconsin-Madison  |

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