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	<title>HIV-1 &#8211; Creative Biolabs Bispecific Antibody Blog</title>
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	<title>HIV-1 &#8211; Creative Biolabs Bispecific Antibody Blog</title>
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		<title>Advancing HIV-1 Therapy: Bispecific Antibodies to Enhance Latent Reservoir Clearance</title>
		<link>https://www.creative-biolabs.com/blog/bsab/advancing-hiv-1-therapy-bispecific-antibodies-to-enhance-latent-reservoir-clearance/</link>
		
		<dc:creator><![CDATA[biobsab]]></dc:creator>
		<pubDate>Sun, 28 Jan 2024 07:55:00 +0000</pubDate>
				<category><![CDATA[Bispecific Antibody Research]]></category>
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		<category><![CDATA[HIV-1]]></category>
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					<description><![CDATA[Antiretroviral therapy can suppress HIV-1 replication, but the persistence of long-lived resting memory CD4+ T cells harboring latent pre-viral HIV-1 DNA prevents a cure. To date, clinical interventions based on Latency Reversal<a class="moretag" href="https://www.creative-biolabs.com/blog/bsab/advancing-hiv-1-therapy-bispecific-antibodies-to-enhance-latent-reservoir-clearance/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Antiretroviral therapy can suppress HIV-1 replication, but the persistence of long-lived resting memory CD4+ T cells harboring latent pre-viral HIV-1 DNA prevents a cure. To date, clinical interventions based on Latency Reversal Agents (LRAs) have not achieved a significant reduction in the latent reservoir, despite observed increases in plasma and cell-associated viral RNA. One method to improve the cell-mediated clearance of HIV-1 infected cells is the use of <a href="/bsab/bispecific-antibody-bsab-development-service.htm" target="_blank" rel="noopener"><span style="color: #0000ff;"><strong>bispecific antibodies</strong></span></a>, with immune therapies targeting HIV-1 infected cells primarily focusing on recruiting CD8+ T cells. However, continuous exposure to HIV-1 antigens may lead to CD8+ T cell exhaustion, and several LRAs have been shown to inhibit the cytolytic potential of CD8+ T cells. Furthermore, cytokine release syndrome has occurred in some clinical trials involving T cell-engaging bispecific antibodies, raising safety concerns.</span></p>
<p><span style="font-size: 15px;">Recently, Professor Nathan L. Board and his team from the Department of Medicine at the Johns Hopkins University School of Medicine in Baltimore, Maryland, USA, reported on two anti-CD16 and HIV-1 envelope protein (Env) single-chain dual antibodies (scDbs), aiming to enhance HIV-1 specific NK cell activity. This suggests that HIV-1 specific scDbs warrant further evaluation as a potential therapy for clearing the latent reservoir.</span></p>
<p><img decoding="async" fetchpriority="high" class="aligncenter  wp-image-467" src="https://www.creative-biolabs.com/blog/bsab/wp-content/uploads/2024/02/41590_2023_1741_Fig1_HTML.png" alt="" width="887" height="370" srcset="https://www.creative-biolabs.com/blog/bsab/wp-content/uploads/2024/02/41590_2023_1741_Fig1_HTML.png 2167w, https://www.creative-biolabs.com/blog/bsab/wp-content/uploads/2024/02/41590_2023_1741_Fig1_HTML-300x125.png 300w, https://www.creative-biolabs.com/blog/bsab/wp-content/uploads/2024/02/41590_2023_1741_Fig1_HTML-1024x427.png 1024w, https://www.creative-biolabs.com/blog/bsab/wp-content/uploads/2024/02/41590_2023_1741_Fig1_HTML-768x320.png 768w, https://www.creative-biolabs.com/blog/bsab/wp-content/uploads/2024/02/41590_2023_1741_Fig1_HTML-1536x641.png 1536w, https://www.creative-biolabs.com/blog/bsab/wp-content/uploads/2024/02/41590_2023_1741_Fig1_HTML-2048x854.png 2048w" sizes="(max-width: 887px) 100vw, 887px" /></p>
<p><span style="font-size: 15px;">The findings indicate that single LRA treatment only led to a modest increase in HIV-1 caRNA transcripts, with the surface density of Env being a critical factor in the elimination of infected cells by other Env-specific immune therapeutic approaches, including those based on bNAb-CAR T cells. Multiple participants were able to effectively clear complete viral reservoir cells, suggesting that PMA + I treatment could induce sufficient Env expression for scDb-mediated clearance. PG16-Db and 3BNC117-Db target non-overlapping Env epitopes, and combining these drugs resulted in a slightly higher average clearance rate of reservoir cells than clearance mediated by a single scDb at the same concentration. scDbs can engage multiple cytolytic immune cell types, complementing the limitations of CD8 T cell-based bispecific antibodies. The shorter half-life of scDbs in humanized mice, possibly due to the absence of an Fc domain—which prolongs the half-life of conventional monoclonal IgG therapies through interaction with neonatal Fc receptors—highlights a potential area for improvement.</span></p>
<p><span style="font-size: 15px;">In summary, PG16-Db and 3BNC117-Db merit further evaluation as therapeutic interventions to reduce the HIV-1 reservoir. Future research could focus on combining these scDbs with other therapeutic approaches to further enhance the clearance of HIV-1 infected cells.</span></p>
<p><span style="color: #808080;">Reference</span></p>
<p><span style="color: #808080; font-size: 14px;">1. Board, Nathan L., et al. &#8220;Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells.&#8221; Nature Immunology (2024): 1-9.</span></p>
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