NSCLC / Paving the Way for More Targeted and Less Toxic Immunotherapies

Each year, the Cancer Center Amsterdam (CCA) Foundation champions cutting-edge cancer research by funding promising proposals from CCA researchers. This ‘seed-funding’ empowers CCA scientists to pursue innovative research directions in support of our goal to cure cancer. With this support, Jouke Annema and Marieke Fransen will compare the safety and feasibility of intranodal versus intratumoral injections of immunotherapy in patients with early-stage Non-Small Cell Lung Cancer.

For the treatment of early-stage Non-Small Cell Lung Cancer (NSCLC), the introduction of immune checkpoint blockers (ICB) has marked a significant milestone. These therapies, designed to stimulate the immune system against cancer cells, have shown promise in improving patient outcomes. However, systemic administration of ICBs carries the risk of significant toxicity, ranging from mild autoimmune reactions to severe, life-threatening conditions caused by the systemic activation of the immune system beyond the tumor.

Localizing Therapy Delivery

An alternative that has been explored in other cancers is the injection of ICBs directly into the tumor mass. This intratumoral approach minimizes systemic exposure by directly targeting the tumor microenvironment to enhance the infiltration and activity of immune cells within the tumor. Studies have demonstrated that this localized approach can reduce toxicity without compromising therapeutic benefits.

With the support of a Cancer Center Amsterdam Foundation Proof-of-Concept grant, Jouke Annema and Marieke Fransen will explore a new approach: the injection of ICB’s directly into Tumor Draining Lymph Nodes (TDLN). These lymph nodes are strategically positioned to intercept and filter lymphatic fluid draining away from the tumor, making them the primary site for the early stages of metastasis.

TDLNs are also crucial sites for the initiation of immune responses against the tumor. “By injecting the ICBs into these lymph nodes, we hypothesize it will trigger a more robust immune response targeted to the tumor without serious systemic side effects,” says Jouke Annema, Professor of Pulmonology.

Intranodal versus Intratumoral

To test this hypothesis, the researchers will use endobronchoscopic delivery techniques, comparing the safety and feasibility of intranodal versus intratumoral injections. “This project combines the strength and expertise of our lung cancer research group and has the potential to introduce new treatment options for early-stage NSCLC,” adds Marieke Fransen, Principal Investigator of Translational ImmunoOncology at Amsterdam UMC.

For more information, contact Marieke Fransen or Jouke Annema.

Project Title: Immune checkpoint targeting of tumor and tumor-draining lymph nodes using endobronchial ultrasound in early-stage non-small cell lung cancer.

Researchers involved at Cancer Center Amsterdam

Jouke Annema

Marieke Fransen

Idris Bahce

Hans Daniels

Tanja de Gruijl

Text by Laura Roy.

This article was created for Cancer Center Amsterdam.

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