Immunotherapy attacking head and neck cancer cells

Head and Neck Cancer Breakthrough: Can Immunotherapy Change the Game?

Rhea Morgan in Health & Wellness November 2025 • 5 min read.

"Discover the latest immunotherapeutic approaches that are revolutionizing the treatment of head and neck cancer, offering new hope and improved outcomes for patients worldwide."

Head and neck squamous cell carcinoma (HNSCC) is a significant global health challenge, ranking as the sixth most common malignancy worldwide. With over 550,000 new cases diagnosed annually, and a staggering 380,000 deaths, the impact of this disease is profound. Traditional risk factors such as tobacco and alcohol use are well-established, but genetic predispositions and viral infections also play critical roles in its development. The need for more effective and less toxic treatments has never been more urgent.

For decades, the standard treatments for HNSCC have included surgery, chemotherapy, and radiation therapy, often combined with cetuximab, an epidermal growth factor receptor (EGFR) inhibitor. While these methods have extended lives, they come at a steep price, with significant toxic side effects and frequent instances of treatment resistance or relapse. The five-year overall survival rate has stubbornly remained around 40-50%, highlighting the limitations of conventional approaches. This reality underscores the critical importance of developing innovative therapies that are both more specific and less harmful.

In recent years, immunotherapy has emerged as a promising frontier in cancer treatment, harnessing the power of the body's own immune system to fight malignant cells. The tumor microenvironment in HNSCC is typically immunosuppressive, allowing cancer cells to evade detection and destruction. Immunotherapeutic strategies aim to reverse this suppression, fostering long-term tumor immunosurveillance and offering new hope for patients. This article explores the innovative immunological treatments under investigation and those already available for clinical use in HNSCC, setting the stage for a new era in cancer care.

Monoclonal Antibodies: Precision Strikes Against Cancer

Immunotherapy attacking head and neck cancer cells

Monoclonal antibodies represent a sophisticated class of drugs designed to target specific proteins on cancer cells, disrupting their growth and spread. In HNSCC, several monoclonal antibodies have shown promise, particularly those targeting the epidermal growth factor receptor (EGFR), a protein overexpressed in about 90% of these cancers. EGFR overexpression is associated with advanced disease stages, poorer patient outcomes, and resistance to chemotherapy and radiation therapy.

Cetuximab (Erbitux) was the first targeted therapy approved for HNSCC, marking a significant milestone in the treatment of this disease. It functions by binding to EGFR, thereby inhibiting its activity and preventing cancer cells from growing. Approved in 2006 for use in combination with radiation therapy for locally advanced HNSCC and as a single agent for recurrent or metastatic (R/M) HNSCC, cetuximab has become a cornerstone of treatment.

Panitumumab: Though approved for metastatic colorectal cancer, panitumumab has been investigated for HNSCC. Clinical trials have shown mixed results, with some improvements in disease control but no significant survival benefits.
Zalutumumab: This novel, fully human antibody has shown promise in early trials, demonstrating reasonable efficacy in patients with platinum-refractory R/M HNSCC. However, it did not improve overall survival in phase III trials.
Nimotuzumab: A humanized antibody with anti-proliferative and anti-angiogenic effects, nimotuzumab has shown effectiveness in combination with chemotherapy and radiation therapy, improving patient survival and tolerability.
ABT-806: This humanized antibody binds to a truncated version of EGFR, showing potential in patients with EGFR gene amplification. Early trials have indicated stable disease in some HNSCC patients.
MEHD7945A: Targeting both EGFR and HER3, this dual-action antibody has undergone phase I trials, showing partial responses in some patients with advanced epithelial tumors.
Sym004: This mixture of two anti-EGFR antibodies has shown some efficacy in patients who have failed other anti-EGFR therapies, with a percentage of patients experiencing stable disease and tumor shrinkage.

While EGFR inhibitors have demonstrated efficacy, researchers continue to explore new ways to enhance their impact and overcome resistance. The development of monoclonal antibodies targeting other growth factor receptors and signaling pathways is an active area of investigation, offering the potential for more tailored and effective treatments.

The Future of Immunotherapy in HNSCC Treatment

Immunotherapy is rapidly evolving as a critical component in the treatment of head and neck cancer, offering targeted, less toxic options that can significantly improve patient outcomes. As research continues and new clinical trials yield results, the integration of these innovative therapies into standard treatment protocols promises to transform the landscape of oncology and provide hope for those affected by this challenging disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.ijom.2018.10.012, Alternate LINK

Title: Clinical Immunotherapeutic Approaches For The Treatment Of Head And Neck Cancer

Subject: Otorhinolaryngology

Journal: International Journal of Oral and Maxillofacial Surgery

Publisher: Elsevier BV

Authors: S. Kareemaghay, M. Tavassoli

Published: 2019-04-01

Everything You Need To Know

What are the main challenges in treating head and neck squamous cell carcinoma (HNSCC) that make new therapies necessary?

The treatment of head and neck squamous cell carcinoma (HNSCC) faces significant challenges, including the high number of new cases and deaths annually, limitations of standard treatments like surgery, chemotherapy, and radiation therapy, significant toxic side effects, and frequent instances of treatment resistance or relapse. The five-year overall survival rate has remained around 40-50%, highlighting the need for innovative and less harmful therapies. Immunosuppression in the tumor microenvironment further complicates treatment, necessitating strategies to reverse this and foster long-term tumor immunosurveillance.

How do monoclonal antibodies work in the treatment of head and neck cancer, and what is the significance of EGFR in this approach?

Monoclonal antibodies are designed to target specific proteins on cancer cells, disrupting their growth and spread. In head and neck squamous cell carcinoma (HNSCC), they often target the epidermal growth factor receptor (EGFR), which is overexpressed in about 90% of HNSCC cases. Overexpression of EGFR is associated with advanced disease stages, poorer patient outcomes, and resistance to chemotherapy and radiation therapy. By binding to EGFR, monoclonal antibodies like cetuximab inhibit its activity, preventing cancer cells from growing. This approach marks a significant advancement, providing a more targeted therapy compared to traditional methods.

Can you elaborate on cetuximab's role in treating HNSCC and how it has impacted patient outcomes since its approval?

Cetuximab (Erbitux) was the first targeted therapy approved for head and neck squamous cell carcinoma (HNSCC). It functions by binding to the epidermal growth factor receptor (EGFR), inhibiting its activity and preventing cancer cells from growing. Approved in 2006, cetuximab is used in combination with radiation therapy for locally advanced HNSCC and as a single agent for recurrent or metastatic (R/M) HNSCC. It has become a cornerstone of treatment, improving outcomes by providing a targeted approach. However, resistance to cetuximab can develop, prompting the exploration of new strategies and monoclonal antibodies targeting other growth factor receptors and signaling pathways.

Besides cetuximab, what other monoclonal antibodies are being explored for HNSCC treatment, and what are their current statuses in clinical trials?

Besides cetuximab, several other monoclonal antibodies are being explored for head and neck squamous cell carcinoma (HNSCC) treatment. Panitumumab has shown mixed results in clinical trials, with some improvements in disease control but no significant survival benefits. Zalutumumab demonstrated reasonable efficacy in early trials for platinum-refractory R/M HNSCC but did not improve overall survival in phase III trials. Nimotuzumab has shown effectiveness in combination with chemotherapy and radiation therapy, improving patient survival and tolerability. ABT-806 shows potential in patients with EGFR gene amplification. MEHD7945A, targeting both EGFR and HER3, has shown partial responses in some patients with advanced epithelial tumors in phase I trials. Sym004 has demonstrated some efficacy in patients who have failed other anti-EGFR therapies, with a percentage of patients experiencing stable disease and tumor shrinkage.

What is the future outlook for immunotherapy in the treatment of HNSCC, and how is it expected to change the landscape of oncology?

Immunotherapy is rapidly evolving as a critical component in the treatment of head and neck squamous cell carcinoma (HNSCC), offering targeted, less toxic options that can significantly improve patient outcomes. The integration of these innovative therapies into standard treatment protocols promises to transform the landscape of oncology. The key lies in harnessing the body's immune system to fight malignant cells and reverse immunosuppression in the tumor microenvironment. As research continues and new clinical trials yield results, the future of immunotherapy in HNSCC involves refining monoclonal antibodies, developing new targeted therapies, and integrating them effectively into treatment regimens to enhance long-term survival rates and reduce the toxic side effects associated with conventional treatments.