J. Ihle et al., ANTIBODY-TARGETED SUPERANTIGENS INDUCE LYSIS OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-NEGATIVE T-CELL LEUKEMIA LINES, Cancer research, 55(3), 1995, pp. 623-628
CTLs bearing certain T-cell receptor V beta-regions are directed by th
e bacterial superantigen Staphylococcus enterotoxin A (SEA) to lyse MH
C class II-positive cells. In order to extend superantigen-dependent c
ytotoxicity to MHC class II-negative carcinoma cells, covalent conjuga
tes of superantigen and mAbs against surface markers of these cells ha
ve been used. We now describe a novel strategy which allows rapid sele
ction of mAb suitable for superantigen targeting against MHC class II-
negative tumor cells. A recombinant fusion protein of protein A and SE
A binding to the mAbs CD7 or CD38 was able to mediate T cell-dependent
lysis of MHC class II-negative Molt-4 and CCRF-CEM acute lymphatic le
ukemia cell Lines. Lysis was dose dependent and correlated with E:T ce
ll ratio. In contrast, SEA alone did not induce any significant lysis.
In order to decrease the MHC class II affinity of the protein A-SEA c
omplex, a point mutation was introduced into SEA (protein A-SEA mu9).
The mutated fusion protein had similar potency as protein A-SEA agains
t Molt-4 cells but was 100-fold less active against MHC class II-posit
ive cells. Considering the efficiency and specificity of the mutated S
EA protein interacting with mAb in targeting T lymphocytes against MHC
class II-negative leukemia cells while only marginally affecting norm
al MHC class II-positive cells, we suggest the development of SEA-mAb
fusion proteins as a potential adjuvant therapy of leukemias.