Cancer-specific cell-surface antigens are ideal targets for monoclonal antibody (mAb)-based immunotherapy but are likely to have previously been identified in transcriptome or proteome analyses. Here, we show that the active conformer of an integrin can serve as a specific therapeutic target for multiple myeloma (MM). We screened >10,000 anti-MM mAb clones and identified MMG49 as an MM-specific mAb specifically recognizing a subset of integrin β molecules. The MMG49 epitope, in the N-terminal region of the β chain, is predicted to be inaccessible in the resting integrin conformer but exposed in the active conformation. Elevated expression and constitutive activation of integrin β conferred high MMG49 reactivity on MM cells, whereas MMG49 binding was scarcely detectable in other cell types including normal integrin β lymphocytes. T cells transduced with MMG49-derived chimeric antigen receptor (CAR) exerted anti-MM effects without damaging normal hematopoietic cells. Thus, MMG49 CAR T cell therapy is promising for MM, and a receptor protein with a rare but physiologically relevant conformation can serve as a cancer immunotherapy target.

Bilirubin and its photoisomers in the biological fluids of a hyperbilirubinaemic newborn infant before and during phototherapy were analyzed by a recently improved HPLC method. In the serum, the percentages of (EZ)- and (ZE)-bilirubin in the total bilirubin concentration before phototherapy were approximately 10% and on average increased over 1.5-fold at 2 h after initiation of phototherapy. The percentage of the (EZ)-cyclobilirubin in the serum bilirubin was under 1%. In the bile, the mean concentration of (ZZ)-bilirubin, derived mainly from (ZE)-bilirubin, nearly tripled during phototherapy. The (EZ)-cyclobilirubin concentration in the bile was very low before phototherapy, increased nearly ten-fold at 3 h after initiation of phototherapy, and was 5- to 6-fold as high as that of (ZZ)-bilirubin. In the urine, upon exposure to light, the urinary concentration of (EZ)-cyclobilirubin is apparently equivalent to half of the biliary concentration of (ZZ)-bilirubin and one-fifth of that of (EZ)-cyclobilirubin. It was concluded that during phototherapy of neonatal hyperbilirubinaemia the structural photoisomer [(EZ)-cyclobilirubin] predominates considerably over the geometric photoisomer [(ZE)-bilirubin].

The partition coefficient, K, of w-phenylalkanols (C6HS(CH2)90H, mp = 0-6) between the bulk water and micelles of sodium dodecyl sulfate (SDS) was determined at 25 O C by a differential spectroscopic method. A new approach for the determination of K has been proposed, taking both the effect of added alkanol on the concentration of monomerically dissolved surfactant in micellar solutions and the fraction of the amount of solubiiized alkanol in that of added alkanol into account, K is found to be independent of the concentration of SDS from just above the critical micelle concentration to high concentration, as well as the concentration of added alkanols. The linear dependence of the free energy change on the alkyl chain length of the alkanols (mP 2 3) on solubilization in micelles calculated from K makes it clear that the contribution of a methylene group to the free energy change is -2.40 k J mol-' in accord with the corresponding value for I-alkanols and that the hydrophobicity of the phenyl group corresponds to that of 3.5 methylene groups. The interaction of the phenylalkanols with SDS has also been discussed. (9) Treiner, C.; Chattopadhyay, A. K.; Bury, R. J. Colloid Interfuce Sci. 1985, 104, 569.

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