The global aim of the current project is to demonstrate that colorectal cancer (CRC) patients can benefit from neo-antigen-targeted therapies.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint consists in determining the percentage of advanced CRC
patients that carry T-cells with the ability to recognize cancer neo-antigens
in an autologous setting. Thereby the percentage of CRC patients that can
benefit from neo-antigen-targeted therapies will also be estimated.
Secondary outcome
NA
Background summary
Following the encouraging clinical responses observed in cancer patients
treated with anti-CTLA-4, -PD-1, or -PD-L1 antibodies, immunotherapy shows
great promise for the treatment of cancer. The blockade of co-inhibitory
pathways in T-cells promotes their activation and triggers anti-tumour
immunity. The latter was shown to be driven against tumour-mutated antigens
(neo-antigens) and to be dependent on the existence of neo-antigen-specific,
activated T-cells, prior to therapeutic intervention. This observation suggests
the complementary enhancement of T-cell responses by means of neo-antigen
vaccination and/or adoptive transfer of neo-antigen-specific T-cell clones.
Study objective
The global aim of the current project is to demonstrate that colorectal cancer
(CRC) patients can benefit from neo-antigen-targeted therapies.
Study design
The coding genomes of CRC tissues will be screened by employing next-generation
sequencing (NGS) in order to identify neo-antigens in a personalized setting.
The identified neo-antigens will be tested for their ability to induce
activation of autologous T-cells isolated from tumour infiltrating lymphocytes
and blood samples. Furthermore, the *immune microenvironment* of the tumours
will be analysed by mass cytometry in order to correlate the occurrence or lack
of neo-antigen recognition by T-cells to the composition of the tumours* immune
cell infiltrate. This is a preclinical research study with a translational
focus.
Study burden and risks
The burden or risks for the patients are minimal as all studies will be
performed on material derived from regular surgical procedures as well as from
blood samples collected through venepuncture.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Tumors analysed will be derived from CRC patients diagnosed with high-risk stage II (IIC), stage III and IV colorectal cancers.
At least 20% of the patients participating in the study should be individuals diagnosed with colorectal cancer until de age of 50 years-old.
Exclusion criteria
Severe anemia (Hb < 6.0 mmol/L)
Design
Recruitment
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL55066.058.15 |