Antitumor effects of fragments (220 and 120 kDa, highly glycosylated peptides) separated from Pronase-treated hen egg white ovomucin were analyzed in a double grafted tumor system. BALB/c mice received simultaneous inoculations of Meth-A fibrosarcoma cells on the right flank (1 × 106 cells) and left flank (2 × 105 cells) on day 0. The two fragments (100 μg/mouse/day) were injected into the right tumor on days 3, 4, and 5, and mice were raised for 21 days. Both fragments cured directly and entirely the right (treated) tumor and inhibited indirectly and slightly the growth of the left (distant) one. Examinations of desialylated 120 kDa fragment indicated that the sialic acid residues in the 120 kDa fragment are not necessarily essential for direct antitumor activity but might be indispensable for regression of distant tumors. The noninhibitory activities in a single tumor system, in which mice received intradermal inoculation of tumor cells only in the left flank, and the increase of immunosuppressive acid protein in serum suggested the slight activation of the immune system. Keywords: Ovomucin; antitumor effect; glycopeptide

CD271 (p75 neurotrophin receptor) plays both positive and negative roles in cancer development, depending on the cell type. We previously reported that CD271 is a marker for tumor initiation and is correlated with a poor prognosis in human hypopharyngeal cancer (HPC). To clarify the role of CD271 in HPC, we established HPC cell lines and knocked down the CD271 expression using siRNA. We found that CD271-knockdown completely suppressed the cells’ tumor-forming capability both in vivo and in vitro. CD271-knockdown also induced cell-cycle arrest in G0 and suppressed ERK phosphorylation. While treatment with an ERK inhibitor only partially inhibited cell growth, CDKN1C, which is required for maintenance of quiescence, was strongly upregulated in CD271-depleted HPC cells, and the double knockdown of CD271 and CDKN1C partially rescued the cells from G0 arrest. In addition, either CD271 depletion or the inhibition of CD271-RhoA signaling by TAT-Pep5 diminished the in vitro migration capability of the HPC cells. Collectively, CD271 initiates tumor formation by increasing the cell proliferation capacity through CDKN1C suppression and ERK-signaling activation, and by accelerating the migration signaling pathway in HPC.

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Abstract:A new type of immuno-cell therapy called BRM-activated killer (BAK) therapy using non-MAC-restricted lymphocytes, CD56-positive cells, was devised. Peripheral blood lymphocytes were selected by immobilization with anti-CD3 monoclonal antibody and cultured for 2 weeks in the presence of IL-2. Thereafter, they were reactivated by 1,000 Vlml of IFN-a for 15 min. Twenty-six outpatients with cancer whose performance status were over 80% on Karnofsky scale were selected for this study. About 6 X 10' BAK cells were returned by intravenous drip infusion, at one month intervals at an outpatient clinic to each of 20 advanced cancer patients in whom many metastatic lesions were found postoperatively, and to 6 patients with no postoperatively detectable metastases. The proportion of CD56-positive cells increased from 20% to 50% with culture. CD56-positive cells have strong cytotoxic activity and produced 20 ng/l0' cells of 13-endorphin, an intracerebral hormone. During the course of BAK therapy, we adopted the Face scale as a QOL indicator. The QOL of all patients remained satisfactory or improved. 13-Endorphin is thought to make patients fell well and maintains good QOL because of its potent analgesic, sedative activity. From that facts that CD56 is a neural cell adhesion molecule and a member of the Ig superfamily, and that the CD56-positive cell produces 13-endorphin, we concluded that the CD56-positive cell is a multifunctional, integrated NIE (neuro-immune-endocrine) cell. Administration of BAK cells allowed all 20 advanced cancer patients with metastases to survive for over one year. All 6 patients receiving the same therapy for prevention of postoperative metastasis have been recurrence-free for one to five years. Key words: CD56-positive cells, Immuno-cell therapy, Prolonged NC, QOLIn the previous report (7), we introduced a new type of immuno-cell therapy called BRM-activated killer (BAK) therapy, which uses lymphocytes that are cultured and activated by immobilized anti-CD3 antibody, IL-2 and IFN-a. We have shown that these activated and proliferated lymphocytes are CD56-positive cells that are found in about half of yoT cells and NK cells, which are non-MHC-restricted killer cells. NK cells are defined as CD 16+ lymphocytes which mediate spontaneous cytotoxicity against several target cell lines and can be c1as-