Influence of organ site and tumor cell type on MUC1-specific tumor immunity.
Keita Morikane,Richard M. Tempero,Connie L. Sivinski,Shimichi Kitajima,Sandra J. Gendler,Michael A. Hollingsworth +5 more
TLDR
It is shown that it is more difficult to produce immune responses to tumors growing at the pancreatic site than the s.c.C.Tg mice, and immune responses evoked by presentation of MUC1 in wild-type mice were effective in rejecting tumor cells in the pancreas of both wild- type and M UC1.Abstract:
We investigated the influence of organ-specific parameters on tolerance and immunity to human MUC1. C57Bl/6 mice (wild-type) and C57Bl/6 transgenic for MUC1 (MUC1.Tg) were challenged in the pancreas with Panc02-MUC1, a C57Bl/6-syngeneic pancreatic cancer cell line expressing human MUC1. Wild-type mice produced immune responses to MUC1 when presented on tumor cells growing in the pancreas; however, the responses to tumors in the pancreas were less effective than responses produced by tumor challenge at the s.c. site. Tumor immunity specific for MUC1 was produced in wild-type mice by two different procedures: (i) s.c. immunization of wild-type mice with a low dose of Panc02-MUC1 or (ii) adoptive transfer of spleen and lymph node cells harvested from wild-type mice previously immunized s.c. with Panc02-MUC1. This demonstrates that immune responses to MUC1 presented at the s.c. site can be detected and adoptively transferred. MUC1.Tg mice were immunologically tolerant to MUC1; however, some immunological protection against orthotopic challenge with Panc02-MUC1 was conferred by adoptive transfer of CD4+ and CD8+ T cells from wild-type mice. These results show that it is more difficult to produce immune responses to tumors growing at the pancreatic site than the s.c. site. Panc02-MUC1 cells growing in the pancreas were accessible to the immune system, and immune responses evoked by s.c. presentation of this molecule in wild-type mice were effective in rejecting tumor cells in the pancreas of both wild-type and MUC1.Tg mice. No effective anti-tumor immune responses against MUC1 were produced in MUC1.Tg mice.read more
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Combined GM-CSF and IL-12 gene therapy synergistically suppresses the growth of orthotopic liver tumors
Chun Jung Chang,Yi Hsiang Chen,Kai-Wen Huang,Hao Wei Cheng,Suit Fong Chan,Kuo Feng Tai,Lih Hwa Hwang +6 more
TL;DR: Results demonstrated that IL‐12, but not GM‐CSF, monotherapy displayed significant therapeutic effects, whereas combination therapy with both cytokines displayed synergistic antitumor effects not only on transplanted tumor models with intermediate or large tumor loads, but also on carcinogen‐induced multifocal liver tumors.
Journal ArticleDOI
MUC1 Vaccines, Comprised of Glycosylated or Non-Glycosylated Peptides or Tumor-Derived MUC1, Can Circumvent Immunoediting to Control Tumor Growth in MUC1 Transgenic Mice
Vani Lakshminarayanan,Nitin T. Supekar,Jie Wei,Dustin B. McCurry,Amylou C. Dueck,Heidi E. Kosiorek,Priyanka Trivedi,Judy M. Bradley,Cathy S. Madsen,Latha B. Pathangey,Dominique B. Hoelzinger,Margreet A. Wolfert,Geert-Jan Boons,Peter A. Cohen,Sandra J. Gendler +14 more
TL;DR: Surprisingly, direct admixture of M UC1-expressing tumor with MUC1-hyperimmune T-cells could not prevent tumor outgrowth or MUC 1 immunoediting, whereas ex vivo activation of the hyperimmune T -cells prior to tumor admixture rendered them curative.
Journal ArticleDOI
An anti-MUC1-antibody-interleukin-2 fusion protein that activates resting NK cells to lysis of MUC1-positive tumour cells.
TL;DR: To activate lymphocytes and natural killer cells, an anti-MUC1-scFv-IL2 fusion protein is generated that contains the C595 single-chain antibody for MUC1 binding, the human IgG1 CH2CH3 domain for protein dimerisation, and interleukin-2 (IL2) for activation of immunological effector cells.
Book ChapterDOI
Modeling Pancreatic Cancer in Animals to Address Specific Hypotheses
Paul J. Grippo,Eric P. Sandgren +1 more
TL;DR: These experimental approaches permit detailed exploration of pancreatic cancer genetics and biology in the whole animal context, thereby mimicking the environment in which human disease occurs.
Journal ArticleDOI
Tumor-specific immunity in MUC1.Tg mice induced by immunization with peptide vaccines from the cytoplasmic tail of CD227 (MUC1)
Karl G. Kohlgraf,Andrew J. Gawron,Michiyo Higashi,Michelle L. VanLith,Xiao Ling Shen,Thomas C. Caffrey,Judy M. Anderson,Michael A. Hollingsworth +7 more
TL;DR: MUC1 peptides may be utilized as an effective anticancer immunotherapeutic and survival can be significantly prolonged in vaccinated MUC1.Tg mice, and confirmed the importance of immunogenic epitopes outside of the TR.
References
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