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Compositions and methods for prostate cancer analysis

A technology for prostate cancer and composition, applied in the field of oncology and cancer diagnosis, capable of solving problems such as sensitivity limitations

Pending Publication Date: 2021-10-26
GENENTECH INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, while CTC diagnostics offer promise for detecting cancer where traditional diagnostic tests fail, current methods are limited by their sensitivity to detect specific tumor markers (e.g., STEAP1)

Method used

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  • Compositions and methods for prostate cancer analysis
  • Compositions and methods for prostate cancer analysis
  • Compositions and methods for prostate cancer analysis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0158] Example 1: Immunofluorescence-based detection of STETC1 expression levels on CTCs

[0159] As shown in this example, immunofluorescence-based assays were able to demonstrate robust detection of STEAP1 on the surface of CTCs, as well as a reduction in the total number of CTCs and STEAP1+CTCs following treatment.

[0160] Samples were processed and analyzed using the four-channel Epic CTC platform as described herein. Blood samples were collected from 42 patients with metastatic castration-resistant prostate cancer (mCRPC) before and after treatment with STEAP1-ADC. After Epic Sciences receives a patient blood sample, the whole blood is lysed and the nucleated cells (approximately 3x10 per slide 6 ) were deposited on microscope slides and frozen at -80°C until analysis. After thawing, slides were stained with an antibody cocktail containing cytokeratin, CD45, DAPI, and 15A5 anti-STEAP1 antibody for assessment of this protein biomarker expression on CTCs. CTCs were iden...

Embodiment 2

[0162] Example 2: Evaluation of ADC Prognosis and Efficacy Using CTC Assays

[0163] Sixty patients with progressive mCRPC received STEAP1-ADC at doses ranging from 0.3-2.8 mg / kg every three weeks. ADC activity was measured by PSA decline and study time >6 months. At ≥2 mg / kg doses, a ≥50% decrease in PSA was observed in 10 / 45 (22%±12.1) patients. ADC activity was most pronounced in patients with IHC 3+ tumors. At ≥ 2 mg / kg, 20 / 45 (44% ± 14.5) patients had unfavorable ≥ 5 CTC counts per 7.5 mL at baseline and were considered evaluable. After the first treatment cycle, unfavorable to favorable CTC count transitions were observed in 11 / 20 (55%±21.8) patients and were significantly associated with PSA decline (Spearman rank r=0.74). By FACS, CTCs showed a readily detectable STEAP1+ signal in EpCAM+ / CD45- events in 14 / 29 samples (49%±31-66%). STEAP1+ events showed an EpCAM+ / CD45- signature ranging from 0-74%, and FACS sorted EpCAM+ / CD45- events demonstrated STEAP1+ RT-PCR expr...

Embodiment 3

[0165] Example 3: Signal amplification protocol increases the dynamic range of the STEAP1 CTC assay.

[0166] STEAP1 signaling was measured in SKBR3 (STEAP1 negative control) and LnCaP (STEAP1 positive control) prostate cancer cell lines in the presence and absence of the amplification protocol ( Figure 9A and 9B ). The cutoff for STEAP+ samples was a signal of >3 when using the non-amplified protocol and a signal >8 when using the amplified protocol. The non-amplified protocol shows a 7.6-fold increase in signal in the LnCaP (positive control) cell line compared to the SKBR3 (negative control) cell line. Scale-up scheme showing a 25-fold increase in signal in the LnCaP (positive control) cell line compared to the SKBR3 (negative control) cell line ( Figure 9A ). For the LnCaP (positive control) cell line, STEAP1 signal amplification resulted in an 8.1-fold increase in mean STEAP1 signal, while only increasing the background (i.e., SKBR3 negative control signal) by 2.4-f...

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Abstract

The present invention relates to compositions and methods for prostate cancer analysis. The present invention provides methods for diagnosing prostate cancer based on the detection of STEAP1 on circulating tumor cells (CTCs) using tyramine signal amplification (TSA). The invention also provides methods of determining the prognosis and efficacy of STEAP1-ADC therapy in patients with prostate cancer, in particular metastatic castration resistant prostate cancer (mCRPC).

Description

[0001] This application is a divisional application of an invention application with a filing date of April 20, 2016, a Chinese application number of 201680029704.9, and an invention title of "composition and method for prostate cancer analysis". [0002] related application [0003] This application claims the benefit of priority to US Provisional Patent Application No. 62 / 150,724, filed April 21, 2015, which is hereby incorporated by reference in its entirety. [0004] field of invention [0005] The present invention relates to the fields of oncology and cancer diagnostics, and more particularly to compositions and methods for prostate cancer screening, staging and treatment monitoring. In specific embodiments, the invention relates to novel prognostic and diagnostic tests and methods of treatment for prostate cancer. [0006] Background of the invention [0007] Prostate cancer is one of the most common cancers in men. While most prostate cancers that develop early are a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/574G01N33/569G01N33/58
CPCG01N33/57434G01N2333/90287G01N2333/4742G01N2333/70589G01N33/57492G01N33/56966G01N33/582A61K47/68031G01N2800/52C07K16/30C07K16/40A61K47/6851A61K47/6871G01N2333/705
Inventor O·卡巴拉I·绍福尔-格鲁斯曼D·马里纽奇F·李S·维尔纳
Owner GENENTECH INC
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