Circulating tumor cell isolation and diagnostics

Aim

The aim is to create a high level of multidisciplinary knowledge of the developing CTC (“liquid biopsy”) field. Based on this, a plan will be defined on how to develop and integrate CTC diagnostics into routine clinical oncology practice to improve quality of patient care. This may include partnerships, collaborations, and research proposals involving both commercial and academic entities.

Scope

Circulating tumor cells (CTCs) are released from primary and metastatic tumors into the blood and have high clinical diagnostic potential in oncology, initially most likely within the context of personalized treatment of patients with metastasized cancer, and in a later phase potentially extending to early cancer diagnostics.

Treatment of cancer is expected to change dramatically in the coming years, as an increasing number of novel targeted drugs, directed at a biological target in the tumor, will become available and partly replace standard chemotherapy treatment. With this development metastasized cancer may be anticipated to turn into a chronic disease where tumor growth can be kept under control for long periods of time. In this approach, it is necessary to monitor the effectiveness of the therapy at regular intervals, and this requires repeated analysis of tumor samples. Unfortunately, while the primary tumor has in general been surgically removed, most metastatic tumors are difficult and dangerous to biopsy, especially when this needs to be done repeatedly. Isolation of CTCs from peripheral blood, as a “liquid biopsy”, is expected to be able to replace biopsies of metastatic tumors for therapy guidance.

To date only one FDA-approved assay (CellSearch from Veridex) is available, the result of which is a CTC-count. The prognostic value of CTC enumeration using this technique has been well established in several tumor types. However, this assay is not suited for prediction of therapy response or resistance, which is expected to become most important in the near future and requires pathology and molecular diagnostics to be performed on the CTCs. For these reasons, worldwide efforts are currently directed at isolating (preferably pure) CTCs from peripheral blood, followed by dedicated (“single cell”) molecular and pathology diagnostics (similar to tissue slide diagnostics), and CTC culture for in vitro determination of drug sensitivity.

The challenge is to develop further techniques enabling viable CTC isolation from a standard blood sample, and to process captured CTCs further into “single cell” pathology, several modalities of molecular diagnostics, and culture. This should ultimately result in a product/device for CTC diagnostics, suited for easy routine use in a general hospital setting.

Major themes and challenges

The following major themes will be focused on:

1. Clinical perspectives and requirements for CTC isolation and diagnostics.

2. CTC enrichment and isolation technologies

3. Single cell diagnostics: pathology and molecular diagnostics (MDx)

Two minor themes will be tackled (no full week attendance required):

4. Clinical trials and regulatory issues

5. Commercialization and the option of pre-competitive collaboration

Format

The workshop will be highly interdisciplinary with – mainly scientific – delegates from diverse fields, among which physicists, chemists, engineers, medical specialists (oncologists, pathologists), representatives from pharmaceutical, in-vitro-diagnostics (IVD) and CTC, companies, a regulatory expert and  a representative from venture capital (Friday only). The program will consist of lectures aimed at exchanging knowledge, and workshops for in-depth discussions and formulating action plans.

Lectures

State-of-the-art lectures will be given mainly in the morning by key note speakers, who will introduce the subject from different angles, both technical as well as clinical, and from the regulatory and business side. They are organized in an informal setting to be highly interactive, directed at initiating discussion and exchanging opinions, and for all lectures there will be an equivalent time for discussion. The intention is to create each day an overview of the theme of the day as an introduction to afternoon workshops. Together all specialists present are provided with a broad common background as to potential technical approaches and the issues to be solved around CTC diagnostics.

Keynote speakers will be asked to enable active interaction during their presentation, and a moderator will be present to guide the interactive discussions, keep track of time, and note down topics that require more detailed discussion after the lecture, or during one of the dedicated workshops. The participants will be stimulated to think along with the speaker and participate in the interactive discussions.

Afternoon workshops

Workshops are dedicated to both technical as well as clinical and diagnostics topics. Some will focus on exchanging ideas, experiences, and research results, while other workshops will aim at obtaining a consensus with respect to experimental approach, clinical applications, commercialization, and next steps (Friday, final workshop). Open interdisciplinary communication and discussion is the goal.

Poster session

The Monday afternoon (17.00-18.00) session will be dedicated to a poster session with short oral presentations (3 minutes). If possible posters will be on view all week starting from the Monday afternoon coffee break

Intellectual property and confidentiality

The combined participation of academic and commercial parties has a risk of introducing issues with regard to intellectual property and confidentiality. However Lorentz conferences are in essence an academic initiative. Discussions should be as open as possible and will be summarized in minutes. In case patentable ideas originate from one of the sessions, inventors and idea will be part of the minutes.