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Rivista di Biologia Molecolare e Biotecnologie

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Minerva Biotecnologica 1998 September;10(3):117-25

lingua: Inglese

Tumor tar­geting ­with immu­no­cy­to­kines. A ­novel ­approach for ­cancer ­therapy

Pertl U. 1, Xiang R. 1, Kleindienst P. 2, Becker J. C. 3, Gillies S. D. 4, Reisfeldd R. A. 1, Lode H. N. 1

1 Scripps ­Research Insti­tute, Depart­ment of Immu­nology, La ­Jolla, CA, USA;
2 ­Institut fur Immun­bi­ol­ogie, ­Albert-Lud­wigs-­Universität, Frei­burg, Ger­many;
3 ­Universitäts Hautk­linik, ­Würzburg, Ger­many;
4 Lex­igen Phar­ma­ceu­ti­cals ­Corp., Lex­ington, MA, USA


The induc­tion of cel­lular ­immune ­response ­capable of erad­i­ca­tion of ­tumor metas­tases is a ­major ­goal in immu­no­therapy of ­cancer. Recom­bi­nant anti­body-cyto­kine ­fusion pro­teins are immu­no­cy­to­kines ­that effec­tively stim­u­late cel­lular ­immune ­responses ­against malig­nan­cies fol­lowing an ­increase in cyto­kine con­cen­tra­tion in the ­tumor micro­en­vi­ron­ment. Erad­i­ca­tion of estab­lished pul­mo­nary and ­hepatic metas­tases of ­murine mel­a­noma and ­colon car­ci­noma in syn­ge­neic ­mouse ­models was ­achieved by the acti­va­tion and expan­sion of ­immune ­effector ­cells ­such as CD8+ T-­cells by inter­leukin-2 immu­no­cy­to­kines. ­This ­effect was fol­lowed by the induc­tion of a per­sis­tent ­tumor pro­tec­tive immu­nity medi­ated by CD8+ ­memory T-­cells. ­These immu­no­cy­to­kines ­were ­equally effec­tive in elim­i­nating estab­lished ­bone ­marrow and ­liver metas­tases of ­murine neu­ro­blas­toma by acti­vating nat­ural ­killer (NK) ­cells. The effec­tive erad­i­ca­tion of metas­tases by immu­no­cy­to­kines ­resulted in sig­nif­i­cant pro­lon­ga­tion in ­life ­span ­over ­that of con­trols ­receiving equiv­a­lent mix­tures of anti­body and inter­leukin-2 ­that ­failed to ­reduce the ­growth of dis­sem­i­nated metas­tases. ­Proof of con­cept was estab­lished indi­cating ­that immu­no­cy­to­kine ­induced acti­va­tion and expan­sion of ­immune ­effector ­cells in the ­tumor micro­en­vi­ron­ment can effec­tively erad­i­cate estab­lished ­tumor metas­tases. ­This prom­ising new ­approach to ­cancer immu­no­therapy may ­lead to clin­ical appli­ca­tions ­that ­improve treat­ment of ­cancer ­patients ­with min­imal ­residual dis­ease in an adju­vant set­ting.

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