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B7-h1 and methods of diagnosis, prognosis, and treatment of cancer

A B7-H1, cancer technology, applied in instruments, measuring devices, scientific instruments, etc., can solve problems such as limiting the immune response of the host

Active Publication Date: 2007-12-05
MAYO FOUND FOR MEDICAL EDUCATION & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, insufficient, inappropriate or suppressive immune molecules present in cancer tissue can limit the host's ability to mount an immune response against cancer

Method used

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  • B7-h1 and methods of diagnosis, prognosis, and treatment of cancer
  • B7-h1 and methods of diagnosis, prognosis, and treatment of cancer
  • B7-h1 and methods of diagnosis, prognosis, and treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] Example 1. Materials and methods

[0104] select patient

[0105] After approval by the Mayo Clinic Institutional Review Board, 429 patients treated with radiation nephrectomy or unilateral nephron-sparing surgery between 2000 and 2002 were identified from the Mayo Clinic Nephrectomy Registry A patient with sporadic clear cell RCC. Because of the pathologic features and patient outcomes of RCC subtypes, all analyzes were restricted to patients with only clear cell RCC, the most common subtype of RCC [Cheville et al (2003) Am.J.Surg.Pathol.27:612 -624]. Since the hB7-H1-specific monoclonal antibody 5H1 (below) can restain fresh-frozen but not paraffin-fixed tissue [Dong et al (2002) Nature Med. 8:793-800], according to the availability of fresh-frozen tissue sexually selected patients.

[0106] pathological features

[0107] Pathological features examined included histologic subtype, tumor size, primary tumor stage, regional lymph node involvement, and distant metas...

Embodiment 2

[0114] Example 2. Survival of RCC Patients Providing Fresh Frozen Tissue Samples

[0115] Of the 429 patients eligible for this trial, 196 (46%) were able to provide fresh-frozen tissue for laboratory studies. Patients with fresh-frozen tissue had larger tumors than those without (mean tumor size 6.0 cm vs. 5.0 cm; p=0.008). However, no other studied characteristics were significantly different between the two groups. Further, cancer-specific survival was not statistically significantly different between patients with and without fresh-frozen tissue (p=0.314).

[0116] At the last round of follow-up, 39 of the 196 study patients had died, including 30 patients who died of clear cell RCC at a mean of 1.1 years (range, 0-2.5) after nephrectomy. Among the 157 patients who were alive at the last round of follow-up, the mean follow-up duration was 2.0 years (range 0-4.1). Estimated cancer-specific survival rates (standard error, number of individuals still at risk) were 91.4% ...

Embodiment 3

[0117] Example 3. Correlation between expression of hB7-H1 in RCC tumor cells and patient outcome

[0118] Immunohistological staining of 196 clear cell RCC samples revealed that either RCC tumor cells did not express hB7-H1, or RCC tumor cells and / or RCC tumor-infiltrating leukocytes expressed hB7-H1 to varying degrees (Tables 1 and 2, and Fig. 1). Furthermore, the proximal tubules in the renal cortex, which are thought to be the origin of RCC tumors, expressed hB7-H1 in none of the 20 normal renal cortex samples studied (Fig. 1).

[0119] The proportion of tumor cells positively stained for hB7-H1 among the 196 samples studied is shown in Table 1. Scatterplots of tumor hB7-H1 expression versus expected risk of death for each patient illustrate that a 10% cutoff is appropriate for these data. Samples from 73 (37.2%) patients had >10% hB7-H1 expression in tumor cells.

[0120] Table 1. Percentage of tumor hB7-H1 expression in 196 clear cell RCC samples

[0121] ...

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Abstract

The invention features methods of diagnosis by assessing B7-H1 expression in a tissue from a subject that has, or is suspected of having, cancer, methods of treatment with agents that interfere with B7-H1-receptor interaction, methods of selecting candidate subjects likely to benefit from cancer immunotherapy, and methods of inhibiting expression of B7-H1.

Description

[0001] This application claims priority from US Provisional Application No.: 60 / 616,590 (filed October 6, 2004), and US Provisional Application: 60 / 642,794 (filed January 11, 2005). The disclosures of US Provisional Application No. 60 / 616,590 and US Provisional Application 60 / 642,794 are hereby incorporated by reference in their entirety. technical field [0002] The present invention relates to immune molecules expressed in cancerous tissues, and in particular to an assessment of the expression of said immune molecules in tumor cells and tumor infiltrating leukocytes. Background technique [0003] An important determinant of cancer initiation and progression is the ability of cancer cells to evade the host immune system. For example, insufficient, inappropriate or suppressive immune molecules present in cancer tissue can limit the host's ability to mount an immune response to cancer. [0004] US Patent No. 6,803,192 and pending US Application Serial Nos. 09 / 649,108, 10 / 127...

Claims

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Application Information

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IPC IPC(8): G01N33/53G01N33/566G01N33/567A61K39/395
Inventor L·程S·E·斯壮姆E·D·权
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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