Vol 6-4 Review Article

Soluble Complement Receptor 1 Therapeutics

Matthew P. Hardy1*, Tony Rowe1, and Sandra Wymann2

1CSL, Bio21 Institute, Victoria, Australia

2CSL, CSL Biological Research Centre, Bern, Switzerland

Human Complement Receptor 1 (CR1/CD35) is a potent negative regulator of the complement system. Its mechanism of action is through interaction with the complement activation fragments, C3b and C4b to mediate decay acceleration of the C3 and C5 convertase complexes as well as cleavage of both ligands into inactive fragments via cofactor activity. The result is inhibition of the classical, lectin, and alternative complement pathways. This article will focus on recombinant soluble forms of CR1 that have been generated as potential therapeutics for complement-mediated disorders. Specifically, we will review and contrast the in vitro and in vivo properties of: sCR1 (BRL55730/TP10/CDX-1135), the soluble full-length extracellular domain of human CR1; sCR1-sLex (TP20), a glyco-engineered version of sCR1 additionally targeted to activated endothelium; APT070 (Mirococept), a CR1 fragment conjugated to a myristoylated peptide to enhance tissue targeting; and CSL040, a soluble truncated version of the CR1 extracellular domain which exhibits altered potency and pharmacokinetic properties as compared to the parental molecule. The data obtained from studies on the effects of these CR1-based molecules in animal models of disease and their therapeutic applications will also be discussed.

DOI: 10.29245/2578-3009/2022/4.1240 View / Download Pdf
Vol 6-3 Original Research Article

Serologic Response of SARS-CoV-2 mRNA-based Vaccines in Patients with Autoimmune Diseases

Kushal Gandhi1#, Nathan Joshua Manales1#, Asley Sanchez1#, Srikanth Mukkera1*, Anusha Ammu1, Janine Klar1, Alex Gibson1, Evangelina Santiago2, Ailena Mulkey2, Jammie Holland2, Maneesh Mannem1, Lakshmi P. Alahari1, and John Garza1,3

1 School of Medicine, Texas Tech University Health Sciences Center (TTUHSC) at the Permian Basin, TX, USA

2 Clinical Research institute at the Permian Basin, Texas Tech University Health Sciences Center – Permian Basin, TX, USA

3 The University of Texas Permian Basin, Odessa, TX, USA

# Authors contributed equally

Background: In the spring of 2021, coronavirus disease 2019 (COVID-19) vaccines were approved and distributed in the United States for the public to combat the COVID-19 pandemic, but their rapid development leaves some questions unanswered. Vaccine efficacy has always been a point of interest for individuals with rheumatological diseases that take immunosuppressants. This study investigates the vaccine efficacy of two COVID-19 mRNA-based vaccines, Moderna and Pfizer, in subjects in West Texas patients with autoimmune diseases.

Materials and Methods: Blood was collected from Texas Tech University employees who received both doses of COVID-19 vaccines within the past nine months. Subjects were separated into either a group with a known history of rheumatic disease (n=18) or those without (n=18). The samples were analyzed for serum immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels using specific enzyme-linked immunoassay kits, and a neutralizing antibody test using a surrogate virus was conducted as well. Results were analyzed using the Mann-Whitney U test (unpaired, two-tailed).

Results: There was no significant difference in serum IgG and IgA levels between the control and rheumatologic disease groups, but there were significant differences in serum IgM levels. All subjects cleared the threshold for the neutralizing antibody test.

Conclusion: The relatively similar serum IgG levels and the 100% detection rate of effective neutralizing antibodies across both groups indicate promising signs of serological response for subjects with autoimmune conditions, but the relatively low serum IgA and IgM levels of the study the group warrants further investigation.

DOI: 10.29245/2578-3009/2022/3.1235 View / Download Pdf
Vol 6-3 Original Research Article

An Acute Inflammation with Special Expression of CD11 & CD4 Produces Abscopal Effect by Intratumoral Injection Chemotherapy Drug with Hapten in Animal Model

Baofa Yu, MD1,2,3,4*, Qiang Fu, MS3, Yan Han, MS3, Jian Zhang3, Dong Chen,MD3

1Immuno Oncology Systems, Inc., San Diego, CA 92122, USA

2TaiMei Baofa Cancer hospital, Dongping, Shandong Province, China, 271500

3Jinan Baofa Cancer hospital, Jinan, Shandong Province, China,250000

4Beijing Baofa Cancer Hospital, Beijing, China

Aim: To study the immunity reaction in tumor by intratumoral injection with a drug PYM and DNP, where it produces abscopal effect by the expression of immunological genes of tumor on home side (left side) while it brings a similar expression of same genes in tumor on opposite side (right side) of mice.

Method: Prepare each tumor on left side of 6 mice and injected intratumoral with a PYM+DNP and PYM control on day 1 and 7. Two day later of day 1, one of groups mice were inoculated with 0.2ml of H22 cells (105/ml) again on the right underarms as opposite side for controls. On day15, the tumor on bilateral sides were excised for qPCR measurement.

Result: It showed that inflammation with the expression of the CoL1a1, CD4, IL12aÂ, TGFb1Â, Elastin, Elastin, Cox2, CD11b/c, CD8, TNFa in different groups; The inflammation in both side of tumor but these is not only a increasing expression of Collal, CD4, IL12aÂ, TGFb1Â, Elastin, NFKB, Cox2, CD11c, CD8 and TNFa in tumor on home side of mice treated with PYM+DNP but also a similar an increasing expression of same genes in tumor on opposite side of mice which not treated at all. In the control group, it showed that inflammation without an expression of all factors related above immunity genes in both tumor on home treated with PYM only and opposite side of mice which not treated at all.

Conclusion: It indicated that PYM and hapten of DNP can induce an inflammation with stimulation of immunity reaction with the expression of the CoL1a1, CD4, IL12aÂ, TGFb1Â, Elastin, Elastin, Cox2, CD11b/c, CD8, TNFaÂ, which resulted in an abscopale effect. PYM can induce an inflammation but without expression of immuno genes, therefore, hapten is playing an important role with PYM in the special immunity reaction.

DOI: 10.29245/2578-3009/2022/3.1236 View / Download Pdf