Immunotherapy vs Targeted Therapy

  • Jhernel Rhudd BSc Medical Biochemistry, University of Leicester
  • Ellen Rogers MSc in Advanced Biological Sciences, University of Exeter

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Introduction

Both immunotherapy and targeted therapy are at the heart of cancer treatment as two relatively advanced treatment options compared to traditional strategies such as surgery, chemotherapy, hormonal therapy and radiotherapy. Immunotherapy treatments aim to harness the patient’s immune system and use it to kill cancer cells, whilst targeted therapy attacks cancer cells directly.

These treatments are most commonly used in precision cancer medicine, where recent developments in gene sequencing and biomarkers allow for the precise choice of therapeutic drugs and tools. All cancers are different - so whilst two patients may both have the same type of cancer (e.g. lung cancer), their cancers may be caused by different genetic mutations. As such, the efficacy and utility of different cancer treatments will vary between cases. Immunotherapy and targeted therapies allow doctors to target different biological pathways, maximising the chances of treatment being successful.1 

It’s important to note that the best treatment option for any given patient will depend on a number of factors, including the type and stage of cancer, the patient’s general health status, and genetic and protein factors. This article will focus on immunotherapy and targeted therapy, discussing how they work, how they are different, and how they can be used to kill cancer cells and generate an antitumour effect. While this article will provide general information, if you have any specific questions about your health and/or treatment, you should see a medical professional. 

What is immunotherapy?

Immunotherapy is designed to strengthen and support your immune system, enhancing its ability to recognise and kill cancer cells. Immunotherapy can be used to either 1) activate your immune system, so that it can kill cancer cells, or 2) suppress it, so that you can safely receive an organ transplant or treatment for autoimmune diseases.

Normally, the immune system recognises, targets, and destroys foreign and abnormal cells to suppress carcinogenesis (the formation of cancerous cells and tumours). Immunotherapy prepares the immune system for combat and improves its ability to identify cancer cells, which can often evade detection by acquiring genetic mutations and presenting proteins on their surface. Furthermore, cancer cells can activate “checkpoint” processes in the cell cycle, preventing the immune system from killing them and allowing them to divide uncontrollably.2 

As cancer cells can evade the immune system in several ways, using immunotherapy to support and increase the potency of the immune system can be extremely effective.

Types of immunotherapy 

Monoclonal antibody therapy

Antibodies are proteins produced by your immune system that act as the first line of defence when your body detects invasion. They bind to specific antigens (molecules on the surface of pathogens or cancer cells) and mark them for destruction. Monoclonal antibody therapy uses lab-made antibodies that are designed to either 1) attack and kill cancer cells or 2) deliver radiation or chemotherapy directly to cancer cells. As such, it is also considered to be a form of targeted therapy.3 

Checkpoint inhibitors

Immune checkpoint proteins are expressed on the surface of T cells (the immune cells that kill invading cells, viruses, and bacteria) and become active after a T cell recognises and binds to cancer cells. Once the T cell has killed a cancer cell, its checkpoint proteins act as an “off switch”, preventing the immune response from becoming too big and damaging healthy cells and tissue.4 Sometimes, cancer cells become capable of flipping the off switch themselves, rendering the immune system inactive and leaving the cancer cells to divide. 

Checkpoint inhibitors prevent the immune system being “switched off” at any time. As a result, T cells can constantly circulate in the bloodstream, detecting cancer cells, and killing them automatically.

Cancer vaccines 

Despite their name, cancer vaccines don’t prevent cancer, but rather train your immune system to recognise cancer cells as foreign and kill them. However, designing cancer vaccines can be very challenging. Unlike viruses and bacteria, cancer cells are very similar to our healthy cells, and cancer cells within the same tumour may express different antigens, making it difficult to select target molecules for the vaccine.5

What is targeted therapy?

Targeted therapy, otherwise known as precision medicine, is another type of cancer treatment. Unlike chemotherapy, which destroys any kind of cell undergoing fast replication (including healthy cells), targeted therapy uses drugs to target precise molecules and proteins that are only found in or on cancer cells. Targeted therapy can interfere with signals used by cancer cells to grow and divide, as well as mark cancer cells so that the immune system can recognise them more easily.6 In most circumstances, targeted therapy is used in combination with chemotherapy, surgery, radiation therapy or hormone therapy.

Examples of targeted therapy 

Angiogenesis inhibitors

Angiogenesis inhibitors are drugs that stop cancer cells from directing the growth of new blood vessels. When tumours grow to a certain size, they start releasing chemical signals (or growth factors) that encourage the formation of new blood vessels through the tumour. These vessels provide the oxygen and nutrients needed to support further cancer cell growth and division. 

Angiogenesis inhibitors are drugs that stop cancer cells from releasing angiogenesis-inducing growth factors, such as vascular endothelial growth factor (VEGF).These drugs bind to growth factor molecules to stop them from being activated and encouraging new blood vessel growth. However, it is important to note that angiogenesis inhibitors do not directly attack or kill cancer cells, so they are normally used in combination with other therapies.8

Monoclonal antibodies (discussed above), if engineered to bind to specific growth factors, can be used as angiogenesis inhibitors.

Comparing immunotherapy and targeted therapy

The main difference between immunotherapy and targeted therapy is that the former focuses on strengthening and supporting your immune system, whilst the latter generally targets specific molecules associated with cancer growth and spread. As such, targeted therapy is more specific than immunotherapy. However, there can be convergence between the two treatments (e.g. monoclonal antibody therapy). 

Currently, doctors do not recommend using either immunotherapy or targeted therapy as the sole treatment for cancer. Consequently, they are usually coupled with other therapies to enhance treatment effectiveness.

When patients are prescribed targeted therapy or targeted therapy, they may need to undergo biomarker testing so that researchers can identify viable target molecules, choose effective medications, and provide insight into how likely the tumour is to respond to the chosen treatment(s).9 However, the use of biomarkers in immunotherapy can be challenging, as immunotherapy targets tend to change over time.

Side effects of immunotherapy VS side effects of targeted therapy:

Although targeted therapy is considered to be less toxic than chemotherapy, it can be accompanied by serious side effects. Similarly, whilst immunotherapy aids the immune system in attacking cancer cells, it also increases the risk of the immune system becoming overactive and/or attacking healthy cells. 

Side effects of immunotherapy include:

  • Diarrhoea
  • Liver damage
  • Difficulties with blood clotting and wound healing
  • High blood pressure

Side effects of targeted therapy include:

  • Diarrhoea
  • Liver damage
  • Skin reactions (itching, rash etc)
  • High or low blood pressure
  • Flu-like symptoms

Furthermore, there is a possibility of cancer cells developing resistance against both immunotherapy and targeted therapy over time, which would cause the treatment to stop being effective. Generally, immunotherapy tends to drive tumour regression for longer; however, its general response rate is limited in comparison to targeted therapy.10

 Whilst immunotherapy tends to cause tumours to shrink more (and for longer periods of time), its general response rate seems to be limited in comparison to targeted therapy.10

Future directions

Combining immunotherapy and targeted therapy

In recent decades, our understanding of the immune system and cancer on a molecular basis has increased drastically. Today, immunotherapy and targeted therapy are considered the best alternative approaches for cancer treatment, and precision medicine has become a popular research area. Whilst immunotherapy and targeted therapy target different pathways, there is potential for them to work well in combination. An increasing number of preclinical and clinical studies have noted that both immunotherapy and targeted therapy exert a potent antitumour effect on several types of cancer - including the skin cancer melanoma.

As our understanding of how melanoma grows, metastasises, and interacts with the human immune system improves, doctors and researchers can suggest new and more advanced therapeutic approaches. For example, recent work looked into using checkpoint inhibitors to inhibit the MAPK pathway, which controls the growth and survival of melanoma cells, and stop benign melanomas from becoming malignant.11 Furthermore, using immunotherapy to target the PD-1 cell death pathway further enhanced the treatments’ antitumour effect and improved long-term tumour regression.12 

Although combining immunotherapy and targeted therapy seems to be very effective, several studies have found that combined therapies have a higher risk of toxicity (due to the use of several different drugs).11 As such, it is essential that combined therapy regimes are carefully designed and dosed, to maximise their efficiency whilst minimising the risk of toxicity and side effects. 

FAQs

Which cancer types do immunotherapy and targeted therapy work against?

Immunotherapy:

  • Bladder cancer
  • Brain cancer
  • Cervical cancer
  • Childhood cancer (leukaemia, lymphoma, brain cancer)

There are also many other cancer types immunotherapy may be applied on, and the FDA have approved several drugs and cancer vaccine options.14

Targeted therapy:

Targeted therapy can be effective against many types of cancer, including head and neck cancer, brain cancer, kidney cancer, melanoma (skin cancer), and lung cancer

How are immunotherapy and targeted therapy delivered?

Immunotherapy can be delivered via:

  • Intravenous (IV) infusion 
  • Pills or capsules (oral)
  • Topical (for skin cancer)

Targeted therapy can be delivered via:

  • Intravenous (IV) infusion
  • Pills or capsules (oral) 
  • Injection under skin (subcutaneously)

Summary

  • Immunotherapy and targeted therapy are two novel cancer treatments
  • Immunotherapy can be used to support and strengthen the immune system (so that it can kill cancer cells more effectively) or to suppress it, so patients can receive organ transplants or treatment for autoimmune disease
  • Targeted therapies can directly attack cancer cells or interfere with their growth mechanisms
  • Due to their different modes of action, immunotherapy and targeted therapy are incomparable but can be used to treat a range of cancers
  • To date, over 5000 clinical trials studying immunotherapy and/or targeted therapy have been carried out
  • There are more than 80 types of targeted therapy available, with the most common being monoclonal antibodies and antitumour inhibitors13
  • Combining immunotherapy and targeted therapy treatments can be very effective against cancer, but it is vital that dosages are carefully calculated to prevent toxicity

References

  1. Johns Hopkins Medicine. Immunotherapy: Precision Medicine in Action [Internet]. [cited 20 Sep 2024]. Available from: https://www.hopkinsmedicine.org/inhealth/about-us/immunotherapy-precision-medicine-action-policy-brief
  2. Cleveland Clinic. Immunotherapy [Internet]. 2024 [cited 20 Sep 2024]. Available from: https://my.clevelandclinic.org/health/treatments/11582-immunotherapy
  3. Mayo Clinic. Monoclonal antibody drugs for cancer: How they work [Internet]. 2023 [cited 20 Sep 2024]. Available from: https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808
  4. Cancer.gov. Immune Checkpoint Inhibitors [Internet]. 2022 [cited 20 Sep 2024]. Available from: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors
  5. Cancer Research Institute. Cancer Vaccines [Internet]. 2023 [cited 20 Sep 2024]. Available from: https://www.cancerresearch.org/treatment-types/cancer-vaccines
  6. Cancer.gov. Targeted Therapy for Cancer [Internet]. 2022 [cited 20 Sep 2024]. Available from: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies
  7. Cancer.gov. Angiogenesis Inhibitors [Internet]. 2018 [cited 20 Sep 2024]. Available from: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet#:~:text=Angiogenesis%20inhibitors%20are%20unique%20cancer,steps%20in%20blood%20vessel%20growth
  8. MD Anderson Cancer Center. Angiogenesis Inhibitors [Internet]. [cited 20 Sep 2024]. Available from: https://www.mdanderson.org/treatment-options/angiogenesis-inhibitors.html
  9. Spencer KR, Wang J, Silk AW, Ganesan S, Kaufman HL, Mehnert JM. Biomarkers for Immunotherapy: Current Developments and Challenges. ASCO Publications. [Internet]. 2016 [cited 20 Sep 2024];(36):e493–503. Available from: https://doi.org/10.1200/edbk_160766
  10. Gillette H. What to Expect from Immunotherapy or Targeted Medications [Internet]. 2024 [cited 20 Sep 2024]. Available from: https://www.healthline.com/health/cancer/cancer-care-treatment-non-chemo-what-to-expect-from-immunotherapy-or-targeted-medications#drawbacks
  11. Yu C, Liu X, Yang J, Zhang M, Jin H, Ma X, et al. Combination of Immunotherapy With Targeted Therapy: Theory and Practice in Metastatic Melanoma. Front. Immunol. [Internet]. 2019 [cited 20 Sep 2024];10. Available from: https://doi.org/10.3389/fimmu.2019.00990
  12. Robert L, Ribas A, Hu-Lieskovan S. Combining targeted therapy with immunotherapy. Can 1+1 equal more than 2? Semin. Immunol. [Internet]. 2016 Feb 1 [cited 20 Sep 2024];28(1):73–80. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1044532316000026
  13. Cleveland Clinic. Targeted Therapy [Internet]. 2024 [cited 20 Sep 2024]. Available from: https://my.clevelandclinic.org/health/treatments/22733-targeted-therapy
  14. Stuart A. Types of Cancer Immunotherapy Can Treat [Internet]. 2024 [cited 20 Sep 2024]. Available from: https://www.webmd.com/cancer/immunotherapy-different-cancers

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