Page 14 - 林口長庚醫研部電子報-2018年9月刊
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NEWSLETTER                                                                                                                                                                                                                     NEWSLETTER
  SEPTEMBER                                                                                                                                                                                                                       SEPTEMBER

  2018                                                                                                                                                                                                                                   2018




      2.Immune correlates of anti-GD2 therapy:
      In collaboration with Dr. Dr. Paul Sondel (Univ of Wisconsin) specific KIR/KIR-

      ligand genotypes [inhibitory KIR2DL2 with its ligand (HLA-C1) together with

      inhibitory KIR3DL1 with its ligand (HLA-Bw4)] were identified to be associated
      with clinical benefit for neuroblastoma patients receiving immunotherapy (Clin Can

      Res, 2017, 24(1): 1–8).Incontrast, for patients with the complementary KIR/KIR-
      ligand genotypes, clinical outcome wasnot significantly different for patients that

      received immunotherapy vs. those receivingisotretinoin alone. Furthermore, HLA-

      Bw4












                                                                                                                                 Reference:
                                                                                                                                 1.Mody R., Naranjo A., Van Ryn C., Yu A.L., London W.B., Shulkin B.L.,

                                                                                                                                 Parisi M.T., Servaes S., Diccianni M.B., Sondel P.M., Maris J.M., Park J.R.,
                                                                                                                                 Bagatell R.* Irinotecan-temozolomide with temsirolimus or Dinutuximab

                                                                                                                                 in children with refractory or relapsed neuroblastoma (COG ANBL1221): an

                                                                                                                                 open-label, randomized, phase 2 trial. Lancet Oncology 2017, 18(7): 946-57.
                                                                                                                                 2.Krbe A.K., Wang W., Carmichael L., Kim K., Mendonca E.A., Song Y., Hess

      status was determined by assessing the genotypes of three separate isoforms of HLA-                                        D., Reville P.K., London W.B., Naranjo A., Hank J.A., Diccianni M.B., Reisfeld

      Bw4: (1) HLA-B-Bw4 with threonine at amino acid 80 (B-Bw4-T80); (2) HLA-B-                                                 R.A., Gillies S.D., Matthay K.K., Cohn S.L., Hogarty M.D., Maris J.M., Park
      Bw4 with isoleucine at amino acid 80 (HLA-B-Bw4-I80); and (3) HLA-A with a Bw4                                             J.R., Ozkaynak F., Gilman A., Yu A.L.*, Sondel P.M.* Neuroblastoma patients’

      epitope (HLA-A-Bw4). patients with KIR3DL1+/A-Bw4+ or with KIR3DL1+/                                                       KIR and KIR-ligand genotypes influence clinical outcome for dinutuximab-

      B-Bw4-T80+ had better outcome on immunotherapy than those randomized to                                                    based immunotherapy: a report from the Children’s Oncology Group. Clinical
      no-immunotherapy, whereas for those with KIR3DL1+/B-Bw4-I80+ there was                                                     Cancer Research 2017, DOI: 10.1158/1078-0432.CCR-17-1767.

      no evidence of  a difference based on immunotherapy vs. no-immunotherapy.                                                  3.Krbe A.K., Wang W., Reville P.K., Carmichael L., Kim K.M., Mendonca E.A.,
      Additionally, we observed differences within treatment types (either within                                                Song Y., Hank J.A., London W.B., Naranjo A., Hong F., Hogarty M.D., Maris

      immunotherapy or no-immunotherapy) that were associated with the genotype                                                  J.M., Park J.R., Ozkaynak M.F., Miller J.S., Gilman A.L., Kahl B., Yu A.L.,

      status for the different KIR3DL1/HLA-Bw4-isoforms. These studies suggest that                                              Sondel P.M.* HLA-Bw4-I-80 isoform differentially influences clinical outcome
      specific HLA-Bw4 isoforms may differentially influence response to these mAb-based                                         as compared to HLA-Bw4-T-80 and HLA-A-Bw4 isoforms in rituximab or

      immunotherapy, further confirming the involvement of KIR-bearing cells in tumor-                                           dinutuximab-based cancer immunotherapy. Frontiers in Immunology 2017,

      reactive mAb-based cancer immunotherapy.  (Frontiers in Immunology, 2017, 8:1-9).                                          8:1-9.





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