In a study published in the journal Biofunctional materials, researchers from the Wits Advanced Drug Delivery Platform (WADDP) Research Unit, Department of Pharmacy and Pharmacology, and the Division of Oncology, Department of Internal Medicine, Infectious Diseases and Oncology Research Institute (IDORI), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg have discussed those challenges involved in the current treatment strategy of Colorectal cancer.

The review examined the potential of combining checkpoint blockade therapy within situ vaccination as an innovative therapeutic strategy to enhance anti-tumour immunity in colorectal cancer, while mitigating the adverse effects associated with existing treatments.

Colorectal cancer (CRC) continues to present significant challenges due to its considerable heterogeneity and complex mechanisms of immune evasion.

Projections indicate that the annual incidence of colorectal cancer will rise to 3,200,000 new cases, reflecting a 63% increase, while the estimated annual mortality rate is anticipated to reach 1,600,000 deaths, marking a 73% rise by the year 2040.

Traditional treatment methods such as surgery, chemotherapy, and radiotherapy continue to be the cornerstone of CRC management.

Recently, immunotherapy has surfaced as a groundbreaking strategy, markedly enhancing outcomes for certain CRC patients.

The clinical application of these methods is constrained by a range of associated adverse effects, such as autoimmune disorders, and efficacy in a few patients.

These therapeutic approaches are also not tumour-specific; they may also impact healthy cells adjacent to the tumour or in different regions of the body.

An effective strategy to improve therapeutic anti-tumour immunity is through the blockade of immune checkpoints.

Tumour cells exploit immune checkpoint pathways to diminish T cell activation, thereby hindering the ability of tumour-specific T lymphocytes to mount an attack against them.

The most efficient and commonly utilised checkpoint inhibitors in clinical settings target the CTLA-4, PD-1, and PD-L1 receptors.

Numerous research findings indicate that inhibiting the PD-1/PD-L1 signalling pathway is a promising strategy for cancer treatment.

This data establishes a robust scientific foundation for the investigation of immune checkpoint inhibitors (ICIs) in the field of clinical oncology.

The targeting of the PD-L1/PD-1 checkpoint as a method of cancer immunotherapy has shown sustained clinical effectiveness across various cancer types, highlighting the critical function of PD-L1/PD-1 in dampening T cell-mediated immune responses against cancer.

Peptides provide a targeted approach for cancer therapy in the field of nanomedicine, reducing negative side effects and improving treatment effectiveness.

Therapeutic peptides functioning as PD-L1/PD-1 pathway inhibitors have been investigated for their possible uses in cancer immunotherapy.

These tumour-homing peptides promote cellular damage and apoptosis by attaching to receptors on tumour cells and transporting therapeutic agents.

This review discussed the use of functionalised nanoparticles with therapeutic peptides and ICIs in the targeted delivery to the tumours.

Nanotechnology is a swiftly advancing discipline anticipated to grow at an exponential rate.

In the realm of pharmaceutics, significant progress has been made in utilising nanotechnology to address the limitations of conventional colon-targeting drug formulations.

Researchers have utilised nanoparticle conjugation to improve the specificity and accuracy of drug delivery, facilitating the targeted administration of anticancer therapies directly to tumours.

Nanomedicine enhances tumour imaging, immunotherapy, and thermal ablation techniques, while also refining the pharmacokinetics and pharmacodynamics of chemotherapy agents.

The surface functionalisation of nanoparticles with peptides to enhance their targeting capabilities and efficacy in cancer therapy is a prevalent approach.

Peptide-functionalised nanostructures are gaining traction in biomedical fields owing to their exceptional specificity, superior biocompatibility, and straightforward accessibility.

This paper also discussed the use of Dendritic cells (DCs) for the In Situ Vaccination (ISV) treatment approach.

ISV is a technique that utilises tumour antigens present at the site of the tumour to elicit adaptive immune responses that are specific to the tumour.

DCs represent the most potent antigen-presenting cells and play a crucial role in cancer immunotherapy, as they possess the ability to initiate, regulate, and maintain specific immune responses against cancer.

DC-based immunotherapy has been shown to reduce adverse effects while improving survival outcomes.

This manuscript further discussed the synergistic potential of Checkpoint Blockade Therapy (CBT) and ISV for the management of colorectal cancer.

While monotherapy is frequently employed, combination therapies that address various tumour pathways are demonstrating greater efficacy.

Notably, the integration of CBT and ISV has exhibited potential benefits.

CBT necessitates the presence of functional T cells to counteract immunosuppressive signals from tumours; however, its effectiveness can be hindered by a lack of tumour-specific T cells.

In contrast, ISV improves both the quantity and quality of these T cells by promoting antigen presentation and immune priming.

Research has shown that the combination of CBT and ISV may enhance antitumor efficacy while reducing the incidence of autoimmune adverse effects.

The implementation of combinatorial therapy is essential for enhancing efficacy while minimising adverse effects.

The integration of checkpoint blockade therapy with in-situ vaccination, employing therapeutic peptides as checkpoint inhibitors alongside dendritic cells for in-situ vaccination, introduces an innovative approach to enhance anti-tumour immunity in colorectal cancer.

This paper was published in Biofuctional Materials (ISSN: 2959-0582), an online multidisciplinary open access journal aiming to provide a peer-reviewed forum for innovation, research and development related to bioactive materials, biomedical materials, bio-inspired materials, bio-fabrications and other bio-functional materials.

The Article Processing Charges (APCs) are entirely waived for papers submitted before the end of 2025.

Source: ELSP