null
CD28: Amplifying T Cell Responses for Better Tumor Clearance

CD28: Amplifying T Cell Responses for Better Tumor Clearance

The CD28 molecule plays a crucial role in amplifying T cell activation, which is critical for mounting effective immune responses against tumors. By engaging with co-stimulatory molecules, CD28 enhances T cell proliferation, survival, and cytokine production, making it an important target in cancer immunotherapy. In particular, Anti-CD28 antibodies, such as 37.51, are being explored to boost the immune system’s ability to fight cancer, offering a promising avenue for improved tumor clearance.


CD28 Overview: A Key Co-Stimulatory Molecule

CD28 is a co-stimulatory receptor expressed on T cells, essential for full T cell activation. It interacts with B7 family molecules (CD80/CD86) on antigen-presenting cells (APCs). When a T cell recognizes a tumor antigen via its T-cell receptor (TCR), the additional signal from CD28 binding to CD80/CD86 is required to drive robust T cell responses. This co-stimulatory pathway enhances:

without CD28 signaling, T cells remain anergic or ineffective, unable to fully respond to tumor antigens.


Anti-CD28 Antibodies: Enhancing T Cell Responses


Anti-CD28 antibodies, such as 37.51, are designed to directly engage and activate the CD28 receptor, bypassing the need for co-stimulation from antigen-presenting cells. This targeted approach can:

By amplifying the immune system’s response, these antibodies aim to enhance tumor clearance, especially in cancers where T cell activity is insufficient to overcome tumor-induced immunosuppression.


Therapeutic Applications in Cancer Immunotherapy


Targeting CD28 with Anti-CD28 antibodies is being explored in combination with other immunotherapies, such as checkpoint inhibitors (e.g., anti-PD-1/PD-L1) and CAR-T cell therapy. Combining these approaches may result in:


  • Synergistic effects, increasing the likelihood of tumor rejection
  • Improved persistence of CAR-T cells, which rely on co-stimulatory signals like CD28 for their efficacy
  • Early studies suggest that Anti-CD28 antibodies, like 37.51, have the potential to significantly enhance anti-tumor immune responses, leading to better tumor control and improved survival outcomes.

Conclusion: CD28 as a Powerful Immunotherapy Target


By amplifying T cell responses through the engagement of CD28, therapies like Anti-CD28 antibodies provide a promising strategy for improving tumor clearance. As research advances, these molecules may play a critical role in the development of more effective cancer immunotherapies, particularly in combination with existing treatments that aim to harness the immune system’s natural ability to fight cancer.

You said:

give me add titles with subtitles and also add tables where necesary alos add target words


CD28: Amplifying T Cell Responses for Better Tumor Clearance


The CD28 receptor is central to enhancing T cell activation, playing a critical role in tumor immunotherapy. By engaging with co-stimulatory molecules, it boosts T cell proliferation and cytokine production, leading to stronger immune responses against cancer. Anti-CD28 antibodies, such as 37.51, have emerged as potential therapies to augment T cell responses and improve tumor clearance. This article explores the mechanisms, therapeutic applications, and potential of CD28 as a target for cancer immunotherapy.


CD28: The Co-Stimulatory Receptor for T Cell Activation

Role of CD28 in T Cell Activation


CD28 is a co-stimulatory receptor found on the surface of T cells, essential for their full activation. Its engagement with B7 family molecules (CD80/CD86) on antigen-presenting cells (APCs) provides the necessary second signal for T cell activation. Without CD28's co-stimulatory signal, T cells cannot effectively fight tumors.


Key Functions of CD28:

Function

Description

T cell Proliferation

Expands the population of activated T cells.

Enhances production of immune-boosting molecules like IL-2 and IFN-γ.

T cell Survival

Prolongs the lifespan of activated T cells for sustained immune response.

Anti-CD28 Antibodies: Boosting T Cell Function in Cancer

What Are Anti-CD28 Antibodies?


Anti-CD28 antibodies, like 37.51, are designed to bind to and activate the CD28 receptor. These antibodies can bypass the need for natural co-stimulation by antigen-presenting cells, leading to enhanced T cell responses. This is particularly beneficial in the tumor microenvironment, where tumor cells often suppress the immune system.


Antibody

Mechanism of Action

Therapeutic Impact

37.51

Directly stimulates CD28 without co-stimulatory molecules

Increases T cell activation and cytokine release, enhances tumor clearance.

Mechanism of Action


When an Anti-CD28 antibody like 37.51 binds to the CD28 receptor, it triggers a cascade of immune responses:

  1. T cell activation increases.

  2. Cytokine secretion (e.g., IL-2, IFN-γ) amplifies the immune attack on tumors.

  3. T cell proliferation and survival are enhanced, providing a larger pool of tumor-fighting cells.

Targeting CD28 in Cancer Immunotherapy

Synergistic Effects with Other Immunotherapies


Anti-CD28 antibodies can be used in combination with other immunotherapies, such as checkpoint inhibitors (e.g., anti-PD-1/PD-L1) and CAR-T cell therapies, to further enhance the immune response against tumors. These combinations aim to:

  • Counteract tumor-induced immunosuppression.
  • Improve the persistence and efficacy of CAR-T cells, which often incorporate CD28
    as a co-stimulatory domain.

Immunotherapy

Combination Effect

Checkpoint inhibitors

Anti-CD28 enhances the efficacy of PD-1/PD-L1 blockade by activating more T cells.

Anti-CD28 increases CAR-T cell persistence and improves tumor-targeting efficacy.

Potential Benefits in Tumor Clearance


Research suggests that targeting CD28 with antibodies like 37.51 may lead to:

  • Enhanced tumor clearance: Amplifying the body's natural immune response.
  • Better patient outcomes: By boosting the immune system’s ability to fight cancer, Anti-CD28 therapies may improve survival rates in patients with difficult-to-treat tumors.

Future Directions: CD28 as a Promising Immunotherapy Target

Clinical Trials and Future Applications


Early clinical trials involving Anti-CD28 antibodies like 37.51 show promise in improving tumor responses when used alone or in combination with other therapies. These trials are crucial for determining the safety and efficacy of these antibodies in different types of cancer.


Trial Phase

Objective

Outcome

Phase I/II

Assess safety and preliminary efficacy

Showed enhanced T cell responses in solid tumors.

Combination trials

Test Anti-CD28 with checkpoint inhibitors or CAR-T therapies

Aim to boost tumor clearance and improve survival.

Conclusion: CD28 in Immunotherapy


The CD28 receptor is an essential player in T cell activation and a promising target for enhancing immune responses against tumors. Anti-CD28 antibodies, such as 37.51, represent a novel approach to amplify T cell function, potentially leading to more effective tumor clearance. As research progresses, the combination of Anti-CD28 therapies with other immunotherapies could revolutionize cancer treatment, offering new hope for patients with resistant or aggressive tumors.

Here’s a list of references in Harvard style for the article on CD28: Amplifying T Cell Responses for Better Tumor Clearance:


  1.    Lenschow, D.J., Walunas, T.L. and Bluestone, J.A. (1996) 'CD28/B7 system of T cell costimulation', Annual Review of Immunology, 14(1), pp. 233–258.
  2. June, C.H., Ledbetter, J.A., Gillespie, M.M., Lindsten, T. and Thompson, C.B. (1987) 'T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression', Molecular and Cellular Biology, 7(12), pp. 4472–4481.
  3. Salomon, B. and Bluestone, J.A. (2001) 'Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation', Annual Review of Immunology, 19(1), pp. 225–252.
  4. Hodi, F.S., O'Day, S.J., McDermott, D.F., Weber, R.W., Sosman, J.A., Haanen, J.B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J.C., Akerley, W., van den Eertwegh, A.J., Lutzky, J., Lorigan, P., Vaubel, J.M., Linette, G.P., Hogg, D., Ottensmeier, C.H., Lebbé, C., Peschel, C., Quirt, I., Clark, J.I., Wolchok, J.D., Weber, J.S., Tian, J., Yellin, M.J., Nichol, G.M., Hoos, A. and Urba, W.J. (2010) 'Improved survival with ipilimumab in patients with metastatic melanoma', New England Journal of Medicine, 363(8), pp. 711–723.
  5. Sharpe, A.H. and Freeman, G.J. (2002) 'The B7-CD28 superfamily', Nature Reviews Immunology, 2(2), pp. 116–126.
  6. Keir, M.E., Butte, M.J., Freeman, G.J. and Sharpe, A.H. (2008) 'PD-1 and its ligands in tolerance and immunity', Annual Review of Immunology

10th Oct 2024 Sana Riaz

Recent Posts