Chimeric Antibodies for Soft Tissue Sarcoma

Overseen By Clinical Trial Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Moonshot Antibodies

Must not be taking: Cytotoxic drugs, Corticosteroids, Live vaccines

Disqualifiers: HIV, Autoimmune diseases, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any cytotoxic treatment within 3 weeks of antibody treatment or systemic therapeutic corticosteroids within 2 weeks prior to starting treatment.

What data supports the effectiveness of the treatment Chimeric Antibodies for Soft Tissue Sarcoma?

Research on chimeric antibodies shows they can effectively target and destroy cancer cells by using the body's immune cells, as seen in studies on multiple myeloma and other cancers. These antibodies combine parts from different species to enhance their ability to fight tumors, suggesting potential benefits for treating soft tissue sarcoma. ^{1 2 3 4 5}

Is there any safety information available for chimeric antibodies used in humans?

Chimeric antibodies have been studied for their ability to target and destroy tumor cells in various cancers, showing different levels of effectiveness in human immune cells. They have been used in clinical settings without significant issues related to human antimouse antibody formation, which suggests a favorable safety profile in humans. ^{4 6 7 8 9}

How do chimeric antibodies differ from other treatments for soft tissue sarcoma?

Chimeric antibodies are unique because they combine mouse and human antibody components, enhancing their ability to target and destroy tumor cells through a process called antibody-dependent cell-mediated cytotoxicity (ADCC). This approach may offer improved effectiveness and reduced side effects compared to traditional treatments, as it leverages the body's immune system to attack cancer cells more efficiently. ^{1 4 10 11 12}

What is the purpose of this trial?

The purpose of this research is to study the safety and effectiveness of investigational antibodies attacking certain areas on the surface of cancer cells so that the body can kill the cancer cells. The antibodies will be made in a laboratory from cells taken from each subject's tumor so they will be made specifically per subject. The first step is to take blood and tumor samples so that the laboratory can produce antibodies specific to each subject's tumor. During this process, the study team will identify specific areas on the cancer cells that are not normally present in healthy cells so that the antibodies can find the cancer cells that should be destroyed. The second step is to deliver the antibodies to each subject through a series of infusions.

Research Team

David Krag, MD

Principal Investigator

Moonshot Antibodies

Eligibility Criteria

This trial is for individuals with advanced (Stage IV) sarcoma or soft tissue sarcoma. Participants must have a tumor that can be used to create personalized chimeric antibodies. Specific eligibility criteria are not provided, but typically include factors like overall health status and prior treatments.

Inclusion Criteria

Post-pubertal study subjects need to agree to use effective birth control methods

Informed written consent required from all subjects

I agree to provide a blood sample and my stored tumor tissue for research.

Exclusion Criteria

Insufficient tumor tissue for whole exome sequencing

Concurrent use of investigational drugs

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Antibody Production

Blood and tumor samples are collected to produce antibodies specific to each subject's tumor

4-6 weeks

Treatment

Participants receive chimeric antibodies through a series of infusions

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Chimeric Antibodies

Trial Overview The trial is testing the safety and effectiveness of custom-made chimeric antibodies designed to target cancer cells in each patient. These antibodies aim to mark the cancer cells so the body's immune system can find and destroy them. The treatment involves taking samples from patients' tumors, creating specific antibodies in a lab, and then administering these through infusions.

Participant Groups

Group I: Treatment group Experimental Treatment 1 Intervention

Treatment with multiple patient-specific mutated cell surface proteins with chimeric antibodies

Who Is Running the Clinical Trial?

Moonshot Antibodies

Lead Sponsor

Trials

1

Recruited

10+

Findings from Research

Chimeric T cells targeting the B-cell antigen CD19 show reduced activity when exposed to T regulatory cells, which can inhibit their ability to proliferate and kill cancer cells.

A modified chimeric receptor that includes the CD28 molecule enhances T cell proliferation and activity even in the presence of T regulatory cells, suggesting a promising approach for improving chimeric T-cell therapy in B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. Loskog, A., Giandomenico, V., Rossig, C., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody. [2021]

2. China pubmed.ncbi.nlm.nih.gov

[In vitro and in vivo functional evaluation of anti-human bladder tumor human-mouse chimeric antibody ch-BDI]. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

A human T cell line engineered to secrete chimeric monoclonal antibody. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Biological activity of human-mouse IgG1, IgG2, IgG3, and IgG4 chimeric monoclonal antibodies with antitumor specificity. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Mechanisms in removal of tumor by antibody. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

A genetically engineered single-gene-encoded anti-TAG72 chimeric antibody secreted from myeloma cells. [2006]

7. United States pubmed.ncbi.nlm.nih.gov

Monoclonal antibody treatment of solid tumors: a coming of age. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Radiolabeled chimeric anti-CEA monoclonal antibody compared with the original mouse monoclonal antibody for surgically treated colorectal carcinoma. [2016]

9. England pubmed.ncbi.nlm.nih.gov

Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Biological characterization of a chimeric mouse-human IgM antibody directed against the 17-1A antigen. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Human IgG2 constant region enhances in vivo stability of anti-tenascin antibody 81C6 compared with its murine parent. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

Tumor-specific genetically engineered murine/human chimeric monoclonal antibody. [2016]