Newer Immuno-oncology Agents

Introduction

Illustrated mechanism of action
Examples of Medication Brand Names (with Images)
Indication
Side Effects
Precautions & Contraindications
Monographs
Reference

History

History of immuno-oncology:

After over a century of development, immuno-oncology has emerged as one of the most effective approaches to cancer treatment. In the late 1890s, William Coley conducted pioneering research into immuno-oncology, demonstrating its potential by successfully using bacterial injections to treat cancer.During the 1980s, novel cancer treatments began to emerge, including adoptive cell therapy, targeted antibodies, and cancer vaccines.

In 1989, the inception of the first chimeric antigen receptor (CAR) marked a significant breakthrough in medical science. Nearly two decades later, in 2012, Carl June employed CAR-T cell therapy to successfully treat a patient afflicted with leukemia. In the 1990s, PD-1/L1 inhibitors were discovered, and these are now the most widely applied type of immunotherapy.

In recent times, immune checkpoint inhibitors like ipilimumab, nivolumab, and atezolizumab have received approval from the Food and Drug Administration (FDA) for the treatment of cancer

Introduction

Immuno-oncology (IO) harnesses the body’s immune system to fight cancer, representing a transformative approach in oncology. Newer agents include immune checkpoint inhibitors (ICIs), bispecific antibodies, T-cell engagers, cancer vaccines, oncolytic viruses, and cellular therapies like CAR-T cells. Among ICIs, pembrolizumab, ipilimumab, and nivolumab are well-established, targeting key immune checkpoints to restore anti-tumor immunity

Mechanism of Action

Newer immuno-oncology agents work by boosting the immune system to better recognize and kill cancer cells. They do this by:

- Blocking proteins that tumors use to suppress immune cells (immune checkpoints).

- Using special antibodies that activate immune cells right at the tumor site.

- Causing cancer cells to die in a way that alerts the immune system.

- Increasing how well cancer cells present themselves to immune cells.

- Employing engineered immune cells (like CAR-T) to directly attack tumors.

- Reducing immune-suppressing cells in the tumor environment.

These strategies help the immune system overcome cancer defenses and improve treatment outcomes.

Pembrolizumab : Anti-PD-1 monoclonal antibody; blocks PD-1 receptor on T-cells, preventing interaction with PD-L1/PD-L2 on tumor cells, restoring T-cell activity.

| Nivolumab : Anti-PD-1 monoclonal antibody; similar to pembrolizumab, inhibits PD-1 checkpoint to reactivate T-cells.

| Ipilimumab : Anti-CTLA-4 monoclonal antibody; blocks CTLA-4 receptor on T-cells, enhancing early T-cell activation and proliferation.

Newer agents Include bispecific antibodies (e.g., BiTEs), co-stimulatory agonists, and second-generation checkpoint inhibitors targeting LAG-3, TIGIT, TIM-3, VISTA, and others, often combined with PD-1/CTLA-4 blockade for synergy

medication Brand Names

Pembrolizumab → Keytruda® (Merck/MSD)

Nivolumab → Opdivo® (Bristol-Myers Squibb)

Cemiplimab → Libtayo® (Regeneron/Sanofi)

Dostarlimab → Jemperli® (GSK)

Retifanlimab → Zynyz® (Incyte)

Ipilimumab → Yervoy® (Bristol-Myers Squibb)

Tremelimumab → Imjudo® (AstraZeneca) (Newer approval for liver cancer with durvalumab)Relatlimab → Opdualag® (Bristol-Myers Squibb) (Combined with nivolumab for melanoma)Teclistamab → Tecvayli® (J&J) (BCMA-targeting for multiple myeloma)

Mosunetuzumab → Lunsumio® (Roche) (CD20/CD3 for lymphoma)

Pembrolizumab → Keytruda

Ipilimumab → Yervoy

Nivolumab → Opdivo

Cemiplimab → Libtayo

Indication

Newer immuno-oncology agents are approved for a wide range of cancer indications, primarily including:

- Non-small cell lung cancer (NSCLC): As first-line or subsequent therapy, often combined with chemotherapy or targeted agents.

- Melanoma: For unresectable or metastatic cases.

- Renal cell carcinoma: Especially intermediate- or poor-risk advanced disease.

- Colorectal cancer: Particularly microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic cases.

- Urothelial carcinoma: Locally advanced or metastatic disease.

- Head and neck squamous cell carcinoma.

- Ovarian and breast cancers: Often in patients with specific genetic mutations (e.g., BRCA).

- Other solid tumors: Including gastric, cervical, hepatocellular carcinoma, Merkel-cell carcinoma, and certain lymphomas.

These agents are used as monotherapy or in combination (e.g., nivolumab plus ipilimumab) and have expanded treatment options across many tumor types, improving survival and response rates.

side effects

Fatigue or just “not feeling well”

Rash and other sikin-related side effects

Diarrhea, loose or bloody stools and/or pain in the abdomen (stomach)

Shortness of breath, coughing and/or chest pain

Nausea, loss of appetite, jaundice and abdominal pain

Hormone-related issues

Eye-related issues

Fever and flu-like symptoms

Kidney-related problems

Numbness or weakness

Infusion reaction.

Precautions and Contraindications

Avoid in patients with active autoimmune diseases or severe immune-related toxicities.

- Pembrolizumab requires PD-L1 biomarker testing for certain indications to optimize patient selection.

- Concomitant use of systemic corticosteroids or antibiotics (e.g., cephalosporins, penicillins) may reduce efficacy of checkpoint inhibitors like nivolumab.

- Careful monitoring for immune-mediated adverse events is essential.

- Newer agents may have specific contraindications depending on their mechanism and combination regimens.