Serial Killer Research Articles

Some aspects of the initial stage of the investigation of serial murders committed on sexual grounds

Статья посвящена анализу проблемных вопросов практики производства отдельных следственных действий для объективной фиксации значимой информации, получаемой при расследовании уголовных дел о серийных убийствах, совершенных на сексуальной почве.

Features in the organization of repeated yard-by-apartment rounds to solve serial murders

Features in the organization of repeated yard-by-apartment rounds to solve serial murders

The Role of Forensic Psychology in Profiling Serial Killers

This research paper delves into the critical role of forensic psychology in profiling serial killers, seeking tounderstand their motives and behaviors to enhance law enforcement efforts and prevention strategies. It exploresthe historical development of profiling, from intuitive judgments to current empirical methodologies, anddelves into the psychological theories underpinning serial killing, such as psychopathy, childhood trauma, andpersonality disorders. The paper discusses the multidimensional approach employed in profiling, combiningcrime scene analysis, victimology, and behavioral analysis, and addresses the potential benefits and limitationsof this investigative tool, highlighting its successes in solving notorious cases but also acknowledging concernsabout biases and subjectivity. Ultimately, the study emphasizes that forensic psychology plays a crucial partin advancing our understanding of the psychological dynamics of serial killers, aiding in their identification,apprehension, and the development of effective prevention measures.this research paper extensively examines thepivotal role of forensic psychology in profiling serial killers, focusing on the historical development, psychologicaltheories, methods used, and the potential benefits and limitations of profiling. By understanding the psychologicaldynamics involved in serial killing, forensic psychology greatly contributes to the identification and apprehensionof dangerous offenders, ultimately enhancing society’s ability to protect against such threats in the future.

Forensic psychological assessment and psychological and forensic portrait of an unknown serial killer

Forensic psychological assessment and psychological and forensic portrait of an unknown serial killer

Post-modernism, Paraphilia, Sadism, Necrophilia, and Sexually Motivated Homicide: An Interdisciplinary Reading of Dennis Cooper’s “Frisk” (1991)

This paper explores the representation of sexually motivated homicide in Dennis Cooper’s “Frisk” (1991) while employing an interdisciplinary framework in methodology, specifically: psychopathology and forensic psychology. First, the novel’s cultural context points to its postmodern strategies, indicative of the psychopathological effects of late capitalist culture. Then the paper turns its attention to the novel’s protagonist, Dennis, who is initially diagnosed with paraphilic disorder as defined by the “Diagnostic and Statistic Manual of Mental Disorders” (2013). Afterward, implementing a typology developed by Anglo-Canadian criminologist Lee Mellor, Dennis is analyzed and categorized as a homicidal necrophilic offender and a homicidal sexual sadist. The detailed investigation of his sexually motivated crimes places the character among the most notorious serial killers in the world.

Troubling Records

Video records created by perpetrators and witnesses of violent crime are increasingly used as evidence in criminal investigations and court proceedings. When these records include the sexual assault, torture, and murder of individuals, they carry significant power to harm those exposed to them, but most importantly, through repeated viewing, they continue to harm those individuals whose suffering is immortalized therein. Using case study methods, including in-depth interviews with those centrally involved in the case, interviews with criminal justice professionals currently working with video evidence of violent crime, and a review of official documents and media reports, this article examines the tragic Canadian case of serial killers Paul Bernardo and Karla Homolka and the videos they recorded of their crimes. We observe that challenging decisions regarding the handling of video records of violent crime during the investigation process, the viewing of such records in court, and access to them by the public and press during the criminal justice process continue to be areas of concern and contestation, pitting principles of open justice against those of victim dignity and privacy. However, challenges regarding access to video records do not end with a trial and an ultimate verdict of guilt or innocence; rather, decisions continue to be made about the preservation or destruction, the storing and cataloguing, and access to archived material. In examining questions regarding the preservation and continued use of the records, we conclude that a responsible and ethical approach to these challenges is best achieved through what Caswell called a survivor-centred approach. We suggest that this approach should include recognizing the traumatic potentiality of records, providing safety and support to those affected, recognizing the potential of records to produce and perpetuate injustice, respecting the autonomy and decisions of survivors, and accepting and facilitating the right to be forgotten.

1920년대 조선과 연쇄살인범으로서 여성의 등장 -최독견의 「난영(亂影)」을 중심으로-

최독견 「난영」은 남편 살해범죄가 하나의 사회문제로 거론될 정도로 빈번하게 발생하고 있던 1920년대 조선 특유의 현실 속에서 발표된 소설이다. 특히 「난영」 발표 3년 전인 1924년에는 일명 ‘본부(本夫)독살미인사건’으로 명명된 미모 여성 김정필에 의한 남편 살해사건이 발생하여 조선 전체가 떠들썩했다. 이 사건은 재판이 끝난 후 십수 년이 지나서도 해당 여성범죄자의 현황을 다룬 취재기사가 이루어질 정도로 조선사회의 이목을 끌었다. 「난영」 역시 이 사건의 영향 아래 창작된 것으로 추정된다. ‘본부독살미인사건’을 기점으로 당시 조선 사회에서는 남편살인사건의 원인에 대한 다양한 분석이 연이어 쏟아져 나오는데, 여성에 대한 조선 사회의 차별, 비합리적 혼인제도 등이 원인으로서 거론되고 있었다. 그런 점에서 당시 조선 특유의 사회문제였던 남편살해사건이 「난영」에서 형상화되고 있는 과정에 대한 고찰은 이 사건에 대한 작가 최독견의 인식, 그리고 여성에 대한 당대 조선 사회의 인식을 읽을 수 있는 중요한 근거가 될 수 있다.

On improving the tactics of searching for missing children under circumstances indicating murder

The article reveals typical organizational and procedural deficiencies that occur during tactical operations to search for missing children. At the same time, situations where there are grounds to believe that abduction and murder of a child have been committed have been analyzed. The peculiarity of the specified tactical operations is connected with the necessity of interaction of forces and means of various agencies, in particular, the National Police, the National Guard, and the State Emergency Service. Cadets, hunters, foresters, volunteers, local residents and other community representatives are also involved in them.
 Proposals for effective planning and conducting of search activities are given, as the efforts of services and units of different specialization and subordination are combined. Special attention was paid in the study to recommendations for ensuring the effective work of canine experts during large-scale searches for people. The capabilities and specialization of service dogs in search operations are determined.
 It is noted that the progress and results of search operations are accompanied by wide publicity through mass media and social networks. The negative consequences of the premature formation of public resonance around the events and the reasons for the danger of this factor for the process of crime investigation are revealed.
 The focus of the study is on recommendations for avoiding and minimizing flaws during search operations. The presented proposals are based on data from the analysis of the practice of investigating the serial murders committed by Serhiy Tkach and Andriy Chikotylo, the circumstances of the search for Daryna Lukyanenko in the village of Ivanivka, Odesa region in June 2019, and other examples from investigative and operational practice.
 The results of the conducted research may be of interest to persons who directly participate in operations to search for missing people, in particular, to police officers, rescue services, volunteers, dog handlers. Separately formulated recommendations can also be used when teaching the educational course of criminology and special courses in this discipline.

Houston Diary. Truman Capote’s unfinished project

In January 1974, The Washington Post was about to print a series of reports on the Houston mass murders perpetrated by the pedophile serial killer Dean Corll. The newspaper announced that the sensationalist reports would be written by Truman Capote, who had already published a well-known documentary novel In Cold Blood (1966). The new project, entitled Houston Diary, promised to become yet another true-crime bestseller. Despite the newspaper’s extensive promotion and the readership’s big interest, the coverage of the trial was never published. Capote refused to proceed with the project, citing ill health, and later would avoid discussing the subject altogether. What was the real reason for the project’s termination and what happened to the writer’s archive pertaining to the ‘Houston case’? Zakharov studied the papers acquired by the New York Public Library in 2019 and found facts that shed light on Capote’s unrealised project to be styled afer In Cold Blood. The article tells of the papers’ discovery and suggests including Houston Diary in Capote’s bibliography as an unfnished work.

Does the Number of Victims Matter in Defining Serial Murder? An Analysis of Homicide Behavioral Characteristics in US Cases from 1985–2016

ABSTRACT Historically, definitions of serial murder in the academic and professional literature vary, sometimes considerably, based on numbers of victims, offender intent, and presence or absence of a psychological “cooling-off period.” To date, an agreed upon definition remains elusive. This study uses a multinomial regression analysis to examine important homicidal behavioral characteristics of serial killers (N = 1,258) in the US concerning offenders who killed two victims compared to counterparts who murdered three, four or five, and six or more victims, respectively. Important case characteristics between categories are observed and discussed. Findings support definitional recommendations that include a minimum victim threshold of three.

Problematic Issues on the Use of Forensic Analysis During Investigation of Crimes

The article purpose is to consider possibilities of applying the method of forensic analysis in the detection and investigation of crimes, to identify problematic issues and ways of optimizing the specified activity of law enforcement agencies. Particular attention is paid to the directions and possibilities of using forensic analysis for the detection and investigation of crimes. Positive examples of the use of forensic analysis in investigative practice for the purpose of uncovering and investigating crimes are presented, as well as the shortcomings of this method are outlined. The effectiveness of the considered method and its availability are noted. The necessity of using forensic analysis in combination with other analytical methods is substantiated. Problematic issues of the application of the method of forensic analysis are identified, ways of solving them are proposed. The need for proper methodical support for the use of forensic analysis in the investigation of crimes was noted. Attention is focused on the fact that the use of forensic analysis requires awareness of its possibilities, in particular, a certain level of knowledge and skills in applying this method during an investigation, gaining experience in using its results in practice, as well as relevant literature and methodological recommendations and access to them by all employees of law enforcement agencies engaged in the detection and investigation of crimes. The need for a comprehensive solution to the problem of methodological support for the use of forensic analysis by all interested state bodies with the involvement of the necessary scientific potential for conducting relevant research and preparing practical recommendations in order to ensure the proper conditions for effective detection and investigation of crimes is emphasized. Keywords: criminalistics; forensic analysis; investigation of crimes; methodological support; serial murders; sexual maniacs; investigative leads.

Single-Cell Profiling Reveals Functional Heterogeneity and Serial Killing in Human Peripheral and Ex Vivo-Generated CD34+ Progenitor-Derived Natural Killer Cells.

Increasing evidence suggests that natural killer (NK) cells are composed of distinct functional subsets. This multifunctional role has made them an attractive choice for anticancer immunotherapy. A functional NK cell repertoire is generated through cellular education, resulting in a heterogeneous NK cell population with distinct capabilities responding to different stimuli. The application of a high-throughput droplet-based microfluidic platform allows monitoring of NK cell-target cell interactions at the single-cell level and in real-time. A variable response of single NK cells toward different target cells is observed, and a distinct population of NK cells (serial killers) capable of inducing multiple target lysis is identified. By assessing the cytotoxic dynamics, it is shown that single umbilical cord blood-derived CD34+ hematopoietic progenitor (HPC)-NK cells display superior antitumor cytotoxicity. With an integrated analysis of cytotoxicity and cytokine secretion, it is shown that target cell interactions augment cytotoxic as well as secretory behavior of NK cells. By providing an integrated assessment of NK cell functions by microfluidics, this study paves the way to further functionally characterize NK cells ultimately aimed to improve cancer immunotherapy.

Why Did He Kill? —A Criminal Psychological Study of Zombie

The novel Zombie by American author Joyce Carol Oates describes the entire self-destructive process of the main character Quentin, who turns from a college student into a ruthless serial killer. This article attempts to interpret the serial killer Quentin in Zombie from the perspective of criminal psychology, mainly the factors influencing the formation of crime, to analyse how Quentin descended into the abyss of crime step by step, which is critical for us to better understand the formation of crime and to take relevant preventive measures.

Charles Manson and his Family: ‘Human monsters, human mutants’

Joan Didion famously described the 1960s as ending abruptly on 9 August 1969 when word spread of the murders of seven people including Hollywood actor Sharon Tate. Fifty years on and the ‘Manson murders’ remain a focal point of interest in American popular culture and media. Netflix’s recent true-crime drama Mindhunter (2017–19) and Quentin Tarantino’s Once upon a Time in Hollywood () represent but two popular examples invoking the crimes. What is consistent across most popular renderings of the murders is the representation of the Family, and of their leader Charles Manson especially, as monstrous, warranting investigation. Utilizing both Jeffrey foundational text ‘Monster culture (seven theses)’ and Natasha Mikles and Joseph Laycock’s () ‘Five further theses on monster theory and religious studies’, this article examines the creation and representation of Charles Manson as a serial killer, a cult leader, but especially as a monster, in the popular culture context.

ADOPTING OSMAN WARNING IN INDONESIA: AN EFFORT TO PROTECT POTENTIAL VICTIMS OF CRIME TARGET

In the development of criminal law globally, experts believe that preventing crime is much better than taking action. This article exemplifies several criminal cases, especially serial murder cases in Indonesia, which show the lack of quality in the crime prevention system in Indonesia. In line with these consequences, this article considers that Indonesia needs a kind of “warning” system to increase efforts to prevent crimes. Furthermore, this article refers to the experience of implementing the Osman Warning in the UK, improving the quality of crime prevention. This article concludes that there are many problems in the crime prevention system in Indonesia. In responding to these problems, this article aims to answer three concerns. First, what are the difficulties in preventing crime in Indonesia? Second, what is the extent of the obligations of law enforcement in preventing crimes? Third, what is the probability of adopting the Osman Warning concept in Indonesia? Furthermore, this article claims that the probability of implementing the Osman Warning in Indonesia is relatively high and is suitable for implementation. Finally, this article provides a view that special regulations are needed in the laws and rules to accommodate the Osman Warning in the criminal law system in Indonesia.

Human trafficking, homicide and current prevention efforts in The United States of America

The article focuses primarily on the question of why human trafficking is often overlooked as a contributing factor in homicide cases. As a case study, the author analyzes one of the most infamous serial murder cases in United States history, the John Wayne Gacy case, in which the human trafficking element remained hidden for almost 40 years. The case is examined from five different perspectives: (1) the prosecution; (2) the defense; (3) the police; (4) the culture; and (5) political corruption. In addition, the piece provides an overview of current efforts in the United States to prevent trafficking in persons, including a summary of the Trafficking Victims Protection Act, the annual Trafficking in Persons Report, with its informative regional and country narratives, and the White House’s National Action Plan to Combat Human Trafficking.

Psychological Profile of a Serial Killer (Based on the Novel “Silence” by Thomas Raab)

The research deals with the issue of genre hybridization in the novel “Silence – Chronicle of a Killer” written by a contemporary Austrian writer Thomas Raab. An examination of the novel's composition and structure, as a text in motion, has been accomplished in the article. The novel “Silence” is an excellent illustration of how the genre of adventure has been adapted to include elements of science fiction. This novel is a love tale, a rural life saga, a formation narrative, and a psychological thriller all in one. As a fictionalized account of the life of a serial murderer with hypersensitive hearing who became a legend for his mental torment and suffering, it serves both as a biography and a thriller. Novelist Raab uses elements from classic horror novels like Frankenstein, German romantics, in particular, G. Kleist, the tale of Casper Hauser, and detective novels like Friedrich Durrenmatt's "Promise" to tell the story of Casper Hauser's disappearance in his book. A new aesthetic experience may be formed at various degrees of identification ranging from naive perception to higher levels of literary reception. Concentration is required for poetic and philosophical substance. Michel Focalut's nomadism, marginality, and authoritarian power rhetoric have been discussed in this article. The novel's ultimate content has been disclosed as the aphesis torment, emotional sublimation, as the birth of an artwork and, at the same time, death of the author, who exposes discourses, accountable for creating texts that are allocated to him.

“A.B.C.” of Immunotherapy in Hematological Malignancies…Promise and Perils

AbstractThe treatment landscape of hematological malignancies has been evolving at an extremely fast pace. Hematological malignancies are diverse and distinct from solid tumors. These constitute challenges, which are also unique opportunities for immunotherapy. The five categories of immunotherapies that have found success in the management of hematological malignancies are allogeneic hematopoietic stem cell transplant, monoclonal antibodies and innovative designs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, and B cell targeting small immunomodulatory molecules. Allogeneic stem cell transplant rightly called our bluntest weapon is the oldest form of successful immunotherapy. Alternate donor transplants and improvement in supportive care have improved the scope of this immunotherapy option. Among monoclonal antibodies, rituximab forms the prototype on which over a dozen other antibodies have been developed. The bispecific T-cell engager (BiTE) blinatumomab engages cytotoxic CD3 T cells with CD19 acute lymphoblastic leukemia (ALL) cells, which is an effective treatment method for relapsed refractory ALL. Immune checkpoint inhibitors have established their role in hematological malignancies with high PD-L1 expression, including relapsed refractory Hodgkin's lymphoma and primary mediastinal B cell lymphoma (BCL). Small immunomodulatory drugs targeting the B cell receptor downstream signaling through BTK inhibitors, SYK inhibitors, PI3K inhibitors (idelalisib), and BCL-2 inhibitors (venetoclax), and immunomodulatory imide drugs (lenalidomide) have also emerged as exciting therapeutic avenues in immunotherapy. CAR T cells are one of the most exciting and promising forms of adoptive immunotherapy. CAR T cells are rightly called living drugs or serial killers to keep patients alive. CAR T cells are genetically engineered, autologous T cells that combine the cytotoxicity of T cells with the antigen-binding specificity of CARs. CARs are antigen-specific but major histocompatibility complex/human leukocyte antigen-independent. There are five approved CAR T cell products for the management of relapsed refractory leukemias, lymphoma, and multiple myeloma. The past and present of immunotherapy have been really exciting and the future looks incredibly promising. The challenges include widening the availability and affordability beyond specialized centers, identification of potentially predictive biomarkers of response, and experience in the management of complications of these novel agents. The combinational approach of multiple immunotherapies might be the way forward to complement the treatment strategies to harness the immune system and to improve survival with good quality of life.

FT555: Off-the-Shelf CAR-NK Cell Therapy Co-Targeting GPRC5D and CD38 for the Treatment of Multiple Myeloma

Recent improvement in patient outcomes with the use of novel cellular immunotherapies for multiple myeloma (MM) has raised the prospect for the emergence of a curative treatment. While BCMA-targeted chimeric antigen receptor (CAR)-T cell therapies have been successful in treating MM, CAR-T cell manufacturing challenges preventing broad patient access and treatment relapse drive the need for additional targeted therapies with emphasis on multi-antigen targeting and off-the-shelf availability. GPRC5D, a tumor-associated orphan G-protein-coupled receptor found to be highly expressed in MM, is a potentially attractive target that has demonstrated promising clinical benefit when targeted via immunotherapy modalities. Here, we describe the development of FT555, an induced pluripotent stem cell (iPSC)-derived CAR-NK (CAR-iNK) cell product with the unique and effective ability to simultaneously co-target GPRC5D and CD38 (an additional tumor-associated antigen of MM) via combination with daratumumab, and which can be mass produced and is available off-the-shelf to support broad patient access. FT555 is a CAR-NK cell derived from an iPSC master cell line that has been multiplexed-engineered at the clonal level to contain four unique modalities; a novel GPRC5D-specific CAR fine-tuned for NK cell biology; a high-affinity, non-cleavable CD16 (hnCD16) to maximize antibody-dependent cellular cytotoxicity (ADCC) when combined with a monoclonal antibody (mAb); a unique IL-15/IL-15 receptor fusion protein (IL15RF) to promote cytokine-independent function; and CD38 knockout to promote NK cell fitness and uniquely prevent anti-CD38 mAb-mediated fratricide. Sourced from a renewable engineered iPSC master cell line, FT555 is a pure population of engineered NK cells (>95% CD56+) exhibiting uniform expression of CAR-GPRC5D (>90%), hnCD16 (>90%) and IL15RF (>90%), with complete elimination of CD38 expression (not detected). In cytotoxicity assays, FT555 shows antigen specificity, dose-dependent potency and importantly, when combined with the anti-CD38 mAb daratumumab, exhibits resistance to fratricide. In a serial restimulation killing assay, FT555 demonstrates persistent tumor-specific activity against GPRC5D-positive MM.1S WT target cells when compared to isogenic GPRC5D knock-out (KO) targets (70.9% control of tumor by AUC against WT targets vs. 3.5% control against GPRC5D KO targets in the third round of stimulation). When used in combination with daratumumab, FT555 targets CD38 and eliminates CAR-resistant GPRC5D KO target cells (57.1% target killing when combined with daratumumab vs. 3.5% target killing in the absence of mAb in the third round of stimulation), demonstrating the capacity for FT555 to target GPRC5D+ and CD38+ cells through CAR and hnCD16 engagement, respectively. In a disseminated xenograft in vivo model of MM where the MM.1S cell line shows comprehensive tumor engraftment, FT555 demonstrates robust killing kinetics and tumor clearance as a single dose, resulting in control of MM progression for up to 42 days and increased survival to 80 days vs. 37 days for the untreated control arm (Figure 1A, 1B, FT555; 99.9% tumor growth inhibition (TGI) at D37, 151% increased lifespan (ILS)). Durability of FT555 is further enhanced with the addition of daratumumab, where tumor growth inhibition deepened and survival improved, with 2 of 5 mice showing complete clearance of tumor cells at Day 80, demonstrating the synergy of anti-tumor activity between CAR and hnCD16 (Figure 1A, 1B, FT555+Dara; 100% TGI at D37, >207% ILS). Furthermore, in a distinct xenograft model of MM, treatment with FT555 resulted in significantly improved TGI against OPM2 tumor targets (FT555; 100% TGI at D51, p < 0.05). Together these studies demonstrate that FT555 is a multiplexed-engineered CAR-NK cell derived from a clonal master iPSC line, which utilizes the intrinsic versatility of NK cells to enable a highly effective combination therapy with daratumumab to simultaneously target both GPRC5D and CD38 in a single, standardized, and scalable off-the-shelf platform. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Senti-202, a Selective, Off-the-Shelf, Preclinical CAR-NK Cell Therapy with CD33 and/or FLT3 Activating CAR, Healthy Cell Protection from Endomucin (EMCN) Inhibitory CAR and Calibrated Release IL-15 for Hematologic Malignancies Including AML

Background: Patients with CD33 and/or FLT3 malignancies, which encompass most myeloid malignancies such as acute myeloid leukemia (AML), have a grim prognosis and a high unmet need. There are no approved cell therapies for patients with AML due to paucity of targets and an immunosuppressive bone marrow milieu. SENTI-202, a preclinical CAR-NK cell is engineered with a logic-gated gene circuit to overcome these challenges. Methods: SENTI-202 is engineered with a FLT3 OR CD33 NOT EMCN logic-gated gene circuit and a proprietary calibrated release IL-15 (crIL-15). These 3 chimeric proteins are engineered onto a natural killer (NK) cell (healthy adult peripheral blood-derived) to create an off-the-shelf chimeric antigen receptor (CAR) NK cell therapy. The bivalent CD33 OR FLT33 (OR GATE) activating CAR (aCAR) enables concurrent targeting of CD33+ and/or FLT3+ AML cells which kills both AML blasts and leukemic stem cells (LSCs) in vitro and in vivo. This concurrent targeting of two tumor antigens could potentially provide longer remission and less chance of relapse. The NOT EMCN (NOT GATE) inhibitory CAR (iCAR) protects healthy EMCN+ hematopoietic stem cells (HSCs) and early hematopoietic progenitor cells (HPCs) from off-tumor toxicity to potentially aid in post-treatment reconstitution of a healthy hematopoietic system. The crIL-15 provides both autocrine and paracrine IL-15 stimulation to the CAR-NK cells (and surrounding immune cells) to promote cell expansion, persistence, and tumor killing. While previous presentations (Garrison et al., 2021) focused on the performance of individual SENTI-202 components in a cell, this presentation focuses on functional data from the complete logic-gated gene circuit and the crIL-15 together in a cell (i.e., the final CAR-NK with all 3 genetic elements). Results: We demonstrated delivery of all circuit components using a single retroviral vector. We then investigated activity of the resulting CAR-NK cells using a traditional in vitro cytotoxicity assay (E:T=1:2; 20hrs) in which SENTI-202 showed >90% killing of leukemia cells (e.g. SEM; P≤0.001), maintained significant serial killing potential (3 rounds; P≤0.0001; P≤0.001; P≤0.001), as well as robust killing against primary AML blasts and LSC-enriched target cell populations. Importantly, SENTI-202 also exhibited significant tumor cell killing and improved survival (P≤0.001) in an MV4-11 xenograft AML mouse model. We investigated the ability of SENTI-202 to reduce off-tumor toxicity toward EMCN+ healthy cells, including primary HSCs. Within in vitro assays, SENTI-202 provided >50% protection to FLT3+ CD33+ model healthy cells that also expressed the EMCN safety antigen, and similar significant protection was maintained through serial protection assays (3 rounds; P≤0.0001; P≤0.001; P≤0.0001). As further evidence of the selectivity imparted using the OR/NOT logic gating approach, in vitro assays with SENTI-202 resulted in killing of leukemia cells but not primary healthy human HSCs and HPCs (~42% protection) (P≤0.01). Finally, in the presence of SENTI-202 in vivo, the NOT GATE protected and enabled significant (P≤0.0001) expansion of EMCN+ FLT3+ CD33+ model healthy cells. Conclusions: In summary, preclinical evaluation of SENTI-202 demonstrated selective killing of CD33 and/or FLT3 expressing AML cell lines while protecting healthy HSCs and HPCs. This selectivity is imparted by the novel logic-gated gene circuit engineered into healthy adult NK cells. Clinical evaluation of SENTI-202 is planned to evaluate the safety and efficacy in patients with hematologic malignancies with high unmet need, including AML.