IMMUNITY TO MELANOMA WITH IL-2-SECRETING ALLOGENEIC CELL
IMMUNITY TO MELANOMA WITH IL-2-SECRETING ALLOGENEIC CELL
批准号:
3200161
负责人:
EDWARD P. COHEN
金额:
$12.97万
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-04-03 至 1995-03-31
中文摘要
尽管它们表达免疫原性决定簇,但B16
黑色素瘤细胞在免疫活性C57BL/6小鼠(H-2b)中逐渐生长。
“逃逸”机制没有建立起来。因为细胞毒性T细胞
众所周知,淋巴细胞能够识别非常广泛的小分子
多肽(在组织相容性类别I的背景下),包括
与新抗原相关的恶性细胞,它可能是生长的
抗基因肿瘤是免疫识别失败的结果,而不是
缺乏与肿瘤相关的决定因素。对这一概念的理解
使肿瘤细胞在免疫活性状态下生长的细胞“缺陷”
接受者可能会对特定的免疫治疗产生重要影响
癌症的威胁。作为一种实验方法,我们使用转染法构建
分泌IL-2的同种异体小鼠成纤维细胞表达黑色素瘤
相关抗原。然后我们测试了细胞的免疫原性
它们在小鼠体内诱导抗黑色素瘤免疫反应的能力
和肿瘤是同基因的。通过转染法制备了该载体
从B16细胞(H-2b)到同种异体LM细胞(H-2k)的基因组DNA
用C57BL/6小鼠。表达黑色素瘤的转基因细胞集落-
分离相关的决定因素,然后感染一个表达
携带IL-2基因的合格质粒。在我们的实验中,C57BL/6
小鼠排斥分泌IL-2、黑色素瘤抗原阳性的同种异体
小鼠细胞对黑色素瘤产生了细胞免疫。这一豁免权
超过了使用非IL-2分泌构建体免疫后的水平,或者
与B16细胞共培养。该提案的目标是确定
为排斥B16黑色素瘤而激活的特定细胞类型
IL-2分泌细胞构建物免疫C57BL/6小鼠
将它们与小鼠免疫后激活的细胞类型进行比较
缺乏一种或多种免疫原性的结构。在……里面
此外,我们计划确定外源性IL-2是否可以替代
细胞间(旁分泌)直接转移IL-2诱导
抗黑色素瘤免疫反应。最后,我们计划确定是否
IL-2分泌载体免疫荷瘤小鼠的实验研究
从而提高了存活率。
英文摘要
In spite of the fact that they express immunogenic determinants, B16
melanoma cells grow progressively in immunocompetent C57BL/6 mice (H-2b).
The mechanism of "escape" is not established. Since cytotoxic T
lymphocytes are known to recognize an extraordinarily wide array of small
peptides (in the context of histocompatibility class I), including
neoantigens associated with malignant cells, it may be that the growth of
antigeneic tumors results from a failure of immune recognition, not from
the absence of tumor associated determinants. An understanding of the
cellular "defect" that enables tumor cells to grow in immunocompetent
recipients could have important implications for the specific immunotherapy
of cancer. As an experimental approach, we used transfection to construct
IL-2-secreting, allogeneic mouse fibroblasts that express melanoma
associated antigens. We then tested the cells' immunogenic properties in
terms of their ability to elicit an anti melanoma immune response in mice
syngeneic with the tumor. The construct was prepared by transfecting
genomic DNA from B16 cells (H-2b) into LM cells (H-2k) which are allogeneic
with C57BL/6 mice. Colonies of transfected cells expressing melanoma-
associated determinants were isolated, and then infected with an expression
competent plasmid carrying the gene for IL-2. In our experiments, C57BL/6
mice rejecting the IL-2-secreting, melanoma antigen-positive allogeneic
mouse cells developed cellular immunity to the melanoma. This immunity
exceeded that following immunization with non-IL-2-secreting constructs, or
with B16 cells. The objectives of the proposal are to determine the
specific cell types activated for rejection of B16 melanoma following
immunization of C57BL/6 mice with the IL-2-secreting cell constructs, and
compare them with cell types activated following immunization of mice with
constructs that lack one or more of the immunogenic properties. In
addition, we plan to determine if exogenous IL-2 can substitute for the
direct cell-to-cell (paracrine) transfer of IL-2 in the induction of an
anti melanoma immune response. Finally, we plan to determine if
immunizations of tumor-bearing mice with the IL-2-secreting constructs
leads to increased survival.
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批准号:6773914
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项目类别:
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资助金额:$27.28万
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财政年份:2003
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负责人:EDWARD P. COHEN
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批准号:7065166
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项目类别:
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资助金额:$26.64万
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财政年份:2003
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负责人:EDWARD P. COHEN
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依托单位:
DNA-based Vaccine for Treatment of Oral Carcinoma
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批准号:6677870
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项目类别:
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资助金额:$26.77万
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财政年份:2003
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依托单位:
IMMUNITY TO MELANOMA WITH IL-2-SECRETING ALLOGENEIC CELL
-
批准号:2096763
-
项目类别:
-
资助金额:$13.3万
-
财政年份:1992
-
负责人:EDWARD P. COHEN
-
依托单位:
IMMUNITY TO MELANOMA WITH IL-2-SECRETING ALLOGENEIC CELL
-
批准号:3200160
-
项目类别:
-
资助金额:$13.71万
-
财政年份:1992
-
负责人:EDWARD P. COHEN
-
依托单位: