SARS-CoV-2 CTLS for COVID-19

Recruiting at 3 trial locations

Overseen By Lauren Harrison, RN, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: New York Medical College

Must not be taking: Steroids, Immunotherapies, Chemotherapy, others

Disqualifiers: Severe disease, GVHD, Respiratory failure, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The 2019 Severe Acute Respiratory Syndrome (SARS) is a global pandemic secondary to a novel coronavirus - SARS-CoV-2. The reported case-fatality ratio for SARS-CoV-2 in the United States is 1.8% with a current death toll of \>300,000 and climbing.4 There is no accepted standard of care or FDA approved therapies for treatment of COVID-19. Virus specific cytotoxic T lymphocytes (CTLs) have become an important part of the treatment landscape for viral reactivation post hematopoietic and solid organ transplantation. Donor derived CTLs have been shown to be safe and effective against a variety of viruses including CMV, EBV, BK and adenovirus. We hypothesize that SARS-CoV-2 specific CTLs generated from a previously infected family donor will be safe and effective for treatment of COVID-19 in family members with mild to moderate disease.

Will I have to stop taking my current medications?

You may need to stop certain medications before joining the trial. Specifically, high-dose steroids, certain immunotherapies, and some types of chemotherapy must be stopped for a specified period before the treatment. It's best to discuss your current medications with the trial team to see if any changes are needed.

What data supports the effectiveness of the SARS-CoV-2 CTLs treatment for COVID-19?

Research shows that SARS-CoV-2-specific T cells, which are part of the immune system, can recognize and attack cells infected with different variants of the virus. This suggests that using these T cells as a treatment could help fight COVID-19, especially in patients who have not responded to other treatments. ^{1 2 3 4 5}

Is SARS-CoV-2 CTLs treatment safe for humans?

The research indicates that SARS-CoV-2-specific T cells, which are part of the immune system, can be safely manufactured and remain stable for several days, suggesting they are generally safe for use in humans. ^{1 2 6 7 8}

How is the SARS-CoV-2 CTLs treatment different from other COVID-19 treatments?

The SARS-CoV-2 CTLs treatment is unique because it uses virus-specific cytotoxic T lymphocytes (CTLs) from recovered COVID-19 patients to help the immune system target and destroy infected cells, unlike most treatments that focus on neutralizing the virus itself. ^{1 2 7 8 9}

Research Team

Mitchell S Cairo, MD

Principal Investigator

New York Medical College

Eligibility Criteria

This trial is for adults aged 18 to 65 with mild to moderate COVID-19 and certain high-risk conditions like chronic lung disease, heart disease, diabetes, obesity, or a weakened immune system. They must be hospitalized but not on oxygen at home prior to admission. A family member who's recently recovered from COVID-19 will donate T cells for the treatment.

Inclusion Criteria

I have a high-risk condition like lung disease, heart disease, diabetes, obesity, or I am immunosuppressed.

I have tested positive for COVID-19 through a swab test.

My donor had COVID-19 symptoms starting over 10 days ago but doesn't need a negative test now.

Exclusion Criteria

I am not pregnant, breastfeeding, and I agree to use birth control during and 6 weeks after treatment.

I am not currently using certain medications or therapies as specified.

I am not listed for an organ transplant nor eligible to receive one.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive family donor derived SARS-CoV-2 cytotoxic T-lymphocytes up to 5 times every 2 weeks along with standard of care for COVID-19

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• SARS-CoV2-CTLS

Trial Overview The study is testing if virus-specific T cells (CTLs) from a family donor can treat COVID-19 in patients with mild to moderate symptoms. Participants will receive standard care plus these CTLs and their effectiveness and safety will be evaluated.

Participant Groups

Group I: SARS-CoV-2 CTLS + Standard of Care Experimental Treatment 2 Interventions

Patients will get family donor derived SARS-CoV-2 cytotoxic t-lymphocytes up to 5 times every 2 weeks along with Standard of care of COVID-19.

Group II: Standard of Care Only Active Control 1 Intervention

Patients will NOT received COVID CTLs but will get standard of care.

SARS-CoV2-CTLS is already approved in United States, European Union for the following indications:

Approved in United States as SARS-CoV-2 CTLs for:

• COVID-19 in immunocompromised individuals

Approved in European Union as SARS-CoV-2 CTLs for:

• COVID-19 in immunocompromised individuals

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

Findings from Research

The study identifies the SARS-CoV-2 M protein as a key target for CD8+ T cells in COVID-19 patients, highlighting the importance of specific T cell responses in relation to disease severity.

Analysis of T cell characteristics revealed that patients with severe COVID-19 had exhausted and less differentiated virus-specific CTLs compared to those with moderate disease, suggesting that T cell dysfunction may influence clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19. Ogura, H., Gohda, J., Lu, X., et al.[2022]

A high percentage (93%) of convalescent COVID-19 donor blood samples met the criteria for generating SARS-CoV-2-specific cytotoxic T-cell lymphocytes (vCTLs), indicating a robust method for T-cell enrichment.

The manufactured SARS-CoV-2-vCTLs exhibited strong functionality, with 79% being IFN-γ+ T cells and a diverse T-cell receptor repertoire, suggesting their potential effectiveness in targeting and treating COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes. Chu, Y., Milner, J., Lamb, M., et al.[2023]

Patients with common variable immunodeficiency (CVID) showed significantly lower levels of SARS-CoV-2-specific CD8 T cells and functional cytotoxic T cells both after natural infection and following mRNA vaccination compared to healthy controls, indicating a compromised immune response.

In contrast, a patient with X-linked agammaglobulinemia (XLA) demonstrated a robust CD8 T cell response after COVID-19 infection, suggesting that certain primary antibody deficiencies may still allow for effective T cell activation in response to viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2-Specific and Functional Cytotoxic CD8 Cells in Primary Antibody Deficiency: Natural Infection and Response to Vaccine. Gupta, S., Agrawal, S., Sandoval, A., et al.[2023]

Adoptive T-cell immunotherapy shows promise for treating viral infections, particularly in immunocompromised patients, by using HLA-matched T cells that can be rapidly expanded from healthy donors.

A study developed a SARS-CoV-2-specific T-cell bank from 12 convalescent individuals, demonstrating that these T cells can effectively target multiple SARS-CoV-2 antigens and remain functional against various virus variants, suggesting a potential treatment for active COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2-specific T cells generated for adoptive immunotherapy are capable of recognizing multiple SARS-CoV-2 variants. Panikkar, A., Lineburg, KE., Raju, J., et al.[2022]

In a study involving 6 immunocompromised patients with persistent COVID-19, the administration of SARS-CoV-2 viral-specific T cells (VSTs) showed partial responses in some patients, but the overall effectiveness and role of VSTs in recovery remain uncertain due to the use of other antiviral treatments.

Two patients fully recovered after receiving VSTs, but it was unclear if the VSTs were the primary factor in their recovery, highlighting the need for further research to understand the potential benefits of VSTs in treating persistent COVID-19 in immunocompromised individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy With Allogeneic Severe Acute Respiratory Syndrome Coronavirus-2-Specific T Cells for Persistent Coronavirus Disease 2019 in Immunocompromised Patients. Haidar, G., Jacobs, JL., Kramer, KH., et al.[2023]

Current COVID-19 vaccines primarily target the Spike protein of the original SARS-CoV-2, making them less effective against variants with mutations in this protein, highlighting the need for vaccine improvements.

The study identified 22 conserved CTL candidate epitopes from the nonstructural polyprotein 1a (pp1a) of SARS-CoV-2, which could be used to develop next-generation vaccines that induce both neutralizing antibodies and CTLs, potentially providing broader protection against emerging variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of HLA-A*24:02-Restricted CTL Candidate Epitopes Derived from the Nonstructural Polyprotein 1a of SARS-CoV-2 and Analysis of Their Conservation Using the Mutation Database of SARS-CoV-2 Variants. Takagi, A., Matsui, M.[2022]

SARS-CoV-2-specific T cells can be successfully manufactured from convalescent COVID-19 patients, showing strong cytotoxic potential and stability for up to 72 hours after collection, which is crucial for potential therapeutic use.

The study demonstrates that these T cells can specifically recognize and kill target cells, suggesting that adoptive transfer of these cells could enhance the immune response in COVID-19 patients at risk of severe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy. Bonifacius, A., Tischer-Zimmermann, S., Santamorena, MM., et al.[2022]

This study identified a highly conserved CTL epitope from the SARS-CoV-2 spike protein that is compatible with most HLA alleles, making it a promising target for enhancing T cell responses in COVID-19 vaccines.

The research utilized web-based tools and laboratory assays to narrow down potential T cell epitopes, highlighting the importance of including T cell responses in vaccine development alongside neutralizing antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein. Jiang, S., Wu, S., Zhao, G., et al.[2022]

The study identified 54 peptides from the SARS-CoV-2 non-structural polyprotein 1a that bind well to the HLA-A*02:01 molecule, with 18 of these peptides successfully inducing cytotoxic T lymphocyte (CTL) responses in mice, indicating potential for effective CTL-based vaccines.

Immunization with a mixture of 10 selected peptides revealed varying immune response patterns among mice, suggesting an immunodominance hierarchy that could inform the design of more effective CTL-targeted COVID-19 vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of HLA-A*02:01-restricted candidate epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2 that may be natural targets of CD8+ T cell recognition in vivo. Takagi, A., Matsui, M.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19. [2022]

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

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

SARS-CoV-2-Specific and Functional Cytotoxic CD8 Cells in Primary Antibody Deficiency: Natural Infection and Response to Vaccine. [2023]

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

SARS-CoV-2-specific T cells generated for adoptive immunotherapy are capable of recognizing multiple SARS-CoV-2 variants. [2022]

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

Therapy With Allogeneic Severe Acute Respiratory Syndrome Coronavirus-2-Specific T Cells for Persistent Coronavirus Disease 2019 in Immunocompromised Patients. [2023]

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

Identification of HLA-A*24:02-Restricted CTL Candidate Epitopes Derived from the Nonstructural Polyprotein 1a of SARS-CoV-2 and Analysis of Their Conservation Using the Mutation Database of SARS-CoV-2 Variants. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy. [2022]

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

Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein. [2022]

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

Identification of HLA-A*02:01-restricted candidate epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2 that may be natural targets of CD8+ T cell recognition in vivo. [2023]