Immunogenicity of Tumor Organoids derived from colorectal, gastric, gynaecological and non-small cell lung cancer, a Feasibility Study

Tumor organoids are three dimensional cultures of cancer stem cells that can
now be cultured on an individual patient basis. In this trial it will be
established whether autologous tumor organoids are immunogenic. If this is the
case it provides a rationale to intiate clinical intervention trials to
evaluate whether tumor organoids can contribute to the development of
patient-specific anti-tumor vaccines or the adoptive transfer of T cells primed
in vitro with autologous tumor organoids.

Establish the immunogenicity of tumor organoids in vitro

This is a protocol aimed at retrieving tumor tissue and blood from patients
with colorectal, gastric, gynaecological and non-small cell lung cancer. Tumor
tissue will be collected by the following means:
- During a biopsy procedure, that is done as part of a clinical study or as
part of standard of care. One of the biopsy specimens retrieved at the biopsy
procedure will be used for organoid culture.
- During a standard of care tumor resection (primary tumor or metastatic
lesion). If possible, healthy tissue will also be retrieved and serve as a
negative control
- For some patients tumor organoid cultures might have been previously derived
using other protocols, for these patients only a blood withdrawal will be
performed.
The blood sample will be used to isolate peripheral blood mononuclear cells
(PBMCs), which can subsequently be used to evaluate the in vitro immunogenic
potential of autologous tumor organoids. A mandatory blood withdrawal of 80cc
will be performed at baseline. An additional three 80cc blood withdrawals are
allowed within the protocol and are optional, not mandatory. For the subsequent
blood withdrawals, an optional serum-sample can be taken, to look for
serological factors that may impact anti-tumor immunity. In this case, the
amount of blood withdrawn for PBMCs can be diminished to a minimum of 40cc.
Between each blood withdrawal, there will be a minimum interval of 1 month.
When sufficient tumor material is present for organoid establishment, Tumor
Infiltrating Lymphocytes (TILs) may be isolated from the remaining resection
material. The reactivity of intratumoral immune cells can be determined using
the matched organoids. Additionally, alternative immune cell subsets may be
isolated from matched patient PBMCs to evaluate their specific reactivity.
Exploration of potential biomarkers associated with immunogenicity may include,
but is not limited to DNA/RNA sequencing or immunohistochemistry. Tumor digest
(where available) can be used to evaluate tumor reactivity of autologous T
cells towards digest and to compare this to the reactivity to tumor organoids.

In this study patients will undergo a blood withdrawal of 80cc. This blood
withdrawal does not pose a risk to patients. Blood withdrawals are only
performed if they are in accordance with the CMRC (Children*s Memorial Research
Center) institutional review board maximum allowable total blood draw volumes.
In some patients, additional blood withdrawal will be performed. This is
limited to three blood withdrawals of 80cc and is optional for the patient.
Tumor tissue for organoid culture will be retrieved during pre-planned
procedures (tumor biopsies or resections) that are performed for other clinical
studies or as part of standard of care. Patients will not benefit from
participation, this trial will however provide important information that can
result in future intervention trials that might benefit patients.