Mouse Anti Human Melanoma-Associated Antigen 4 Hybridoma [DQUD-NBHFB5-3]

Analysis of antibody responses to self-antigens has driven the development of the field of tumor immunology, with the identification of many protein targets found in cancer but with limited expression in normal tissues. Protein microarray technologies offer an unprecedented platform to assay the serological response of cancer patients to tumor antigens in a comprehensive fashion, against many proteins simultaneously. We developed an array containing 329 full-length proteins, originally identified as antigenic in various cancer patients by serological expression cloning (SEREX), that were immobilized as folded, functional products accessible for antibody binding. To validate the use of these microarrays, we selected 31 sera from non-small cell lung cancer patients previously known to react to the following antigens by ELISA: LAGE-1/CrAG2, MAGEA4, TP53, SSX and SOX2. These sera were compared with 22 sera from healthy donors for reactivity against a series of antigens present on microarrays. The sensitivity and specificity of the arrays compared favorably with standard ELISA techniques (94% concordance). We present here a stringent strategy for data analysis and normalization that is applicable to protein arrays in general, and describe findings suggesting that this approach is suitable for defining potential antigenic targets for cancer vaccine development, serum antibody signatures with clinical value, characterization of predictive serum markers for experimental therapeutics, and eventually for the serological definition of the cancer proteome (seromics). (C) 2008 Elsevier B.V. All rights reserved.

Multiple myeloma (MM) is an almost always incurable malignancy of plasma cells. Despite the advent of new therapies, most patients eventually relapse or become treatment-refractory. Consequently, therapies with nonoverlapping mechanisms of action that are nontoxic and provide long-term benefit to patients with MM are greatly needed. To this end, we clinically tested an autologous multitumor-associated antigen (mTAA)-specific T cell product for the treatment of patients with high-risk, relapsed or refractory MM. In this study, we expanded polyclonal T cells from 23 patients with MM. T cells whose native T cell receptors were reactive toward five myeloma-expressed target TAAs (PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1) were enriched ex vivo. To date, we have administered escalating doses of these nonengineered mTAA-specific T cells (0.5 x 10(7) to 2 x 10(7) cells/m(2)) to 21 patients with MM, 9 of whom were at high risk of relapse after a median of 3 lines of prior therapy and 12 with active, relapsed or refractory disease after a median of 3.5 prior lines. The cells were well tolerated, with only two transient, grade III infusion-related adverse events. Furthermore, patients with active relapsed or refractory myeloma enjoyed a longer than expected progression-free survival and responders included three patients who achieved objective responses concomitant with detection of functional TAA-reactive T cell clonotypes derived from the infused mTAA product.