Oncotarget: Improved therapeutic efficacy of unmodified anti-tumor antibodies

The cover for issue 2 of

Oncotarget

features Figure 4, ”

Combination therapy TA99/ICB reduced the lung tumor burden in the B16 model of metastases,

” published in ”


Improved therapeutic efficacy of unmodified anti-tumor antibodies by immune checkpoint blockade and kinase targeted therapy in mouse models of melanoma


” by Pérez-Lorenzo, et al. which reported that here, the authors showed that removing immune suppression and enhancing stimulatory signals increased the anti-tumor activity of unmodified TA99 antibodies with a significant reduction of growth of solid tumors and lung metastases in mouse models of

melanoma

.

Immune checkpoint blockade enhanced the efficacy of TA99, which was associated with greater CD8 /Foxp3 , NK1.1 and dendritic cell infiltrates, suggestive of an increased anti-tumor innate and adaptive immune responses.

Moreover, they found an improved therapeutic effect when YUMM tumor-bearing mice were treated with TA99 combined with MEKi and immune checkpoint blockade.

The

Oncotarget

findings suggest that MEKi induced an increased expression of tumor-associated antigens, which in combination with anti-tumor antibodies, generated a robust adaptive anti-tumor response that was sustained by immune checkpoint inhibition therapy.

The

Oncotarget

findings suggest that MEKi induced an increased expression of tumor-associated antigens, which in combination with anti-tumor antibodies, generated a robust adaptive anti-tumor response that was sustained by immune checkpoint inhibition therapy.

The authors postulate that combining anti-tumor antibodies with standard-of-care strategies such as immune checkpoint blockade or targeted therapy, will improve therapeutic outcomes in cancer.

Dr. Angela M. Christiano from The Columbia University said, ”

It is well accepted that tumor development and progression is usually controlled by immunosurveillance mechanisms in which specific and non-specific immunological responses are constantly mounted against tumor cells.

”

Passive administration of anti-tumor antibodies generally functions by targeting malignant cells through IgG-mediated antibody-dependent cellular

cytotoxicity

, which is a rapid but relatively short-acting anti-tumor response.

Alternatively, they and others also demonstrated that the administration of anti-tumor antibodies induces long-lasting FcR-dependent tumor specific immunity in the host, with kinetics consistent with an induced adaptive immune response against the tumor.

In this model, anti-tumor antibodies, alone or in combination with chemotherapy, will promote innate cell-mediated ADCC, and the capture and processing of antigens by antigen presenting cells, with the subsequent stimulation and homing of antigen-specific effector T lymphocytes to the tumor site, leading to tumor elimination, a phenomenon the researchers and others referred to as the “


vaccinal effect


”.

With the use of the B16 and YUMM mouse models of melanoma and the anti-TYRP1 mouse monoclonal antibody TA99, we demonstrated that the therapeutic effects of these unmodified anti-tumor antibodies can be enhanced by ICB through the stimulation of both innate and adaptive anti-tumor immune responses.

In addition, they found that the MEK inhibitor -induced increased expression of melanosomal antigens further enhanced the anti-melanoma response to combination therapy with anti-tumor antibodies and immune checkpoint blockade in mouse models of melanoma.

The Christiano Research Team concluded in their

Oncotarget


Research Paper

, ”

Together with our preclinical data, these results invite further clinical investigation of unmodified anti-tumor antibodies in combination with ICB and targeted therapies, and may represent promising and innovative therapeutic interventions for the successful management of patients with advanced melanoma and other cancers.

”

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DOI

–

https:/

27868

Full text

–

https:/

Correspondence to

– Angela M. Christiano –

[email protected]

Keywords

–


anti-tumor antibodies

,

targeted therapy

,

immunotherapy

,

combination therapies

,

melanoma

About Oncotarget

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